MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Seminars in Immunology' source. Wed, 08 Feb 2012 06:43:03 +0100 http://www.medworm.com/index.php?rid=5659653&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22296734%26dopt%3DAbstract Authors: Robertson SJ, Rubino SJ, Geddes K, Philpott DJ Abstract Nod-like receptors (NLRs) for detecting microbial invaders are features of many plant and animal families. Although broadly similar in form and function, intimate co-evolutionary events with environmental microbes have shaped specific classes of NLRs in different types of hosts. Details of the roles of different NLRs in signaling cellular immune responses to invading microbes are only beginning to emerge. This review will discuss the current understanding of NLRs in plants, invertebrates, and mammals, with emphasis on their role in regulating NF-κB and inflammasome activity in mammals. PMID: 22296734 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5659653 Mon, 30 Jan 2012 05:00:00 +0100 5659653 http://www.medworm.com/index.php?rid=5659654&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22284578%26dopt%3DAbstract Authors: Charroux B, Royet J Abstract Millions of people suffer from inflammatory diseases of the intestine, some of them potentiating gastrointestinal cancer. These gut-associated pathologies arise from imbalanced interactions between the host gut epithelia and resident or ingested microbes, interactions that are still poorly understood at the molecular level. Drosophila has been a very powerful model to study development and diseases. Its relatively simple tissue organization and sophisticated genetics are some of the advantages of using it as an experimental model to dissect gut-microbe interactions. Recent progress made in various research fields such as Drosophila microbiota composition, gut epithelium structure or gut immune reactions led us to believe that Drosophila is beco... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5659654 Wed, 25 Jan 2012 05:00:00 +0100 5659654 http://www.medworm.com/index.php?rid=5623932&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265028%26dopt%3DAbstract Authors: Burcelin R, Garidou L, Pomié C Abstract Over the last decades the rising occurrence of metabolic diseases throughout the world points to the failure of preventive and therapeutic strategies and of the corresponding molecular and physiological concepts. Therefore, a new paradigm needs to be elucidated. Very recently the intimate cross talk of the intestinal microbiota with the host immune system has opened new avenues. The large diversity of the intestinal microbes' genome, i.e. the metagenome, and the extreme plasticity of the immune system provide a unique balance which, when finely tuned, maintains a steady homeostasis. The discovery that a new microbiota repertoire is one of the causes responsible for the onset of metabolic disease suggests that the relationship with t... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5623932 Thu, 19 Jan 2012 05:00:00 +0100 5623932 http://www.medworm.com/index.php?rid=5536530&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177884%26dopt%3DAbstract Authors: Cerf-Bensussan N, Eberl G PMID: 22177884 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5536530 Fri, 16 Dec 2011 05:00:00 +0100 5536530 http://www.medworm.com/index.php?rid=5536523&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178452%26dopt%3DAbstract Authors: Molloy MJ, Bouladoux N, Belkaid Y Abstract Recent studies have highlighted the fundamental role of commensal microbes in the maintenance of host homeostasis. For instance, commensals can play a major role in the control of host defense, metabolism and tissue development. Over the past few years, abundant experimental data also support their central role in the induction and control of both innate and adaptive responses. It is now clearly established that commensals are not equal in their capacity to trigger control regulatory or effector responses, however, the molecular basis of these differences has only recently begun to be explored. This review will discuss recent findings evaluating how commensals shape both effector and regulatory responses at steady state and during... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5536523 Thu, 15 Dec 2011 05:00:00 +0100 5536523 http://www.medworm.com/index.php?rid=5536531&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172550%26dopt%3DAbstract Authors: Tanoue T, Honda K Abstract CD4(+) regulatory T (Treg) cells expressing the transcription factor forkhead box P3 (Foxp3) play a critical role in maintaining immunological homeostasis. Treg cells are highly abundant in the mouse intestinal lamina propria, particularly in the colon. Recent studies using germ-free and gnotobiotic mice have revealed that specific components of the intestinal microbiota influence the number and function of Treg cells. Substantial changes in the composition of microbiota have been associated with inflammatory bowel disease. In this review, we will discuss recent findings that associate intestinal microbiota in mice with Treg responses and with the maintenance of intestinal immune homeostasis. PMID: 22172550 [PubMed - as supplied by publisher]... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5536531 Tue, 13 Dec 2011 05:00:00 +0100 5536531 http://www.medworm.com/index.php?rid=5536532&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154556%26dopt%3DAbstract Authors: McFall-Ngai M, Heath-Heckman EA, Gillette AA, Peyer SM, Harvie EA Abstract Recent research on a wide variety of systems has demonstrated that animals generally coevolve with their microbial symbionts. Although such relationships are most often established anew each generation, the partners associate with fidelity, i.e., they form exclusive alliances within the context of rich communities of non-symbiotic environmental microbes. The mechanisms by which this exclusivity is achieved and maintained remain largely unknown. Studies of the model symbiosis between the Hawaiian squid Euprymna scolopes and the marine luminous bacterium Vibrio fischeri provide evidence that the interplay between evolutionarily conserved features of the innate immune system, most notably MAMP/PRR inte... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5536532 Wed, 07 Dec 2011 05:00:00 +0100 5536532 http://www.medworm.com/index.php?rid=5536538&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22153981%26dopt%3DAbstract Authors: Everly MJ, Terasaki PI Abstract The current evidence clearly points towards donor specific alloantibody as a major cause of allograft loss. In order to mitigate allograft loss due to antibodies, treating the source of antibody production, the plasma cell is essential. Therapies that lack effect on the terminally differentiated (long-lived) plasma cell, such as rituximab, intravenous immune globulin and, plasmapheresis were the therapies used prior to 2007. In studies, their ability to remove antibody was found to be incomplete and/or cost prohibitive. In 2007, a proteasome inhibitor, bortezomib, was used for the first time in transplant due to its ability to deplete plasma cells. Through multiple case reports it has demonstrated consistent success in DSA reduction and remo... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5536538 Mon, 05 Dec 2011 05:00:00 +0100 5536538 http://www.medworm.com/index.php?rid=5494018&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138187%26dopt%3DAbstract Authors: Geuking MB, McCoy KD, Macpherson AJ Abstract The large production of immunoglobulin (Ig)A is energetically costly. The fact that evolution retained this apparent luxury of intestinal class switch recombination to IgA within the human population strongly indicates that there must be a critical specific function of IgA for survival of the species. The function of IgA has been investigated in a series of different models that will be discussed here. While IgA has clear protective functions against toxins or in the context of intestinal viral infections, the function of IgA specific for non-pathogenic commensal bacteria remains unclear. In the context of the current literature we present a hypothesis where secretory IgA integrates as an additional layer of immune function into... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5494018 Fri, 02 Dec 2011 05:00:00 +0100 5494018 http://www.medworm.com/index.php?rid=5494017&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138188%26dopt%3DAbstract Authors: Duerr CU, Hornef MW Abstract Only one single layer of epithelial cells separates the densely colonized and environmentally exposed intestinal lumen from the largely sterile subepithelial tissue. Together with the overlaying mucus and the subepithelial mucosal immune system the epithelium has evolved to maintain homeostasis in the presence of the enteric microbiota. It also contributes to rapid and efficient antimicrobial host defence in the event of infection with pathogenic microorganisms. Both, epithelial antimicrobial host defence and homeostasis rely on signalling pathways induced by innate immune receptors demonstrating the active role of epithelial cells in the host-microbial interplay. The interaction of epithelial cells with professional immune cells illustrates th... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5494017 Fri, 02 Dec 2011 05:00:00 +0100 5494017 http://www.medworm.com/index.php?rid=5494022&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22136693%26dopt%3DAbstract Authors: Jiang S PMID: 22136693 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5494022 Thu, 01 Dec 2011 05:00:00 +0100 5494022 http://www.medworm.com/index.php?rid=5494021&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22136694%26dopt%3DAbstract Authors: Kim HJ, Cantor H Abstract Mounting an efficient immune response to pathogens while avoiding damage to host tissues is the central task of the immune system. Emerging evidence has highlighted the contribution of the CD8(+) lineage of regulatory T cells to the maintenance of self-tolerance. Specific recognition of the MHC class Ib molecule Qa-1 complexed to peptides expressed by activated CD4(+) T cells by regulatory CD8(+) T cells triggers an inhibitory interaction that prevents autoimmune responses. Conversely, defective Qa-1-restricted CD8(+) regulatory activity can result in development of systemic autoimmune disease. Here, we review recent research into the cellular and molecular basis of these regulatory T cells, their mechanism of suppressive activity and the potentia... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5494021 Thu, 01 Dec 2011 05:00:00 +0100 5494021 http://www.medworm.com/index.php?rid=5494020&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137187%26dopt%3DAbstract Authors: Kwun J, Bulut P, Kim E, Dar W, Oh B, Ruhil R, Iwakoshi N, Knechtle SJ Abstract The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models m... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5494020 Wed, 30 Nov 2011 05:00:00 +0100 5494020 http://www.medworm.com/index.php?rid=5494019&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22137188%26dopt%3DAbstract Authors: Swiatczak B, Rescigno M Abstract Coordination of immune responses in the gut is a complex task. In order to fight pathogens and maintain a defined population of commensal microbes, the mucosal immune system has to coordinate information from the external (luminal) and internal (abluminal) environment and respond accordingly. Dendritic cells (DCs) are crucial cell types involved in this process as they integrate these signals and direct immunogenic or tolerogenic responses. Here, we review how various functions of DCs depend on microbial stimuli and how these stimuli influence the course of immune activation. PMID: 22137188 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5494019 Wed, 30 Nov 2011 05:00:00 +0100 5494019 http://www.medworm.com/index.php?rid=5422623&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055883%26dopt%3DAbstract Authors: Yamaguchi T, Wing JB, Sakaguchi S Abstract Foxp3-expressing regulatory T cells (Tregs) play a crucial role in maintaining immune tolerance and homeostasis. One of the key issues for understanding Treg immunobiology is to determine how they suppress excessive or aberrant immune responses. Although a number of molecules have been reported to contribute to Treg suppressive function, the importance and precise role of each molecule is not clear. In this review, we propose and discuss that two modes of suppression can be distinguished. In the physiological and steady state, activation of naïve T cells can be suppressed by natural Tregs via deprivation of activation signals including CD28 signal and IL-2 from antigen-reactive T cells, keeping the latter in a naïve state in lym... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5422623 Wed, 02 Nov 2011 04:00:00 +0100 5422623 http://www.medworm.com/index.php?rid=5381732&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22051115%26dopt%3DAbstract Authors: Smith RN, Colvin RB Abstract Alloantibodies clearly cause acute antibody mediated rejection, and all available evidence supports their pathogenic etiology in the development of chronic alloantibody mediated rejection (CAMR). But the slow evolution of this disease, the on-going immunosuppression, the variations in titer of alloantibodies, and variation in antigenic targets all complicate identifying which dynamic factors are most important clinically and pathologically. This review highlights the pathological factors related to the diagnosis of CAMR, the time course and natural history of this disease. What is known about CAMR pathogenesis is discussed including alloantibodies, the role of complement, gene activation, and Fc effector cell function. Therapy, which is problem... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5381732 Tue, 01 Nov 2011 04:00:00 +0100 5381732 http://www.medworm.com/index.php?rid=5381733&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22035649%26dopt%3DAbstract Authors: Zarkhin V, Sarwal MM Abstract Transplantation is the preferred therapy for the end stage organ disease. Since the introduction of organ transplantation into medical practice in 1953 [1], significant progress has been achieved in patient and graft survival rates due to improvements in surgical techniques and more targeted immunosuppressive medications [2]. Nevertheless, current gaps in the management of the transplant patient stem from an incomplete understanding about the heterogeneity of the injury response in organ transplantation, at different rates and different time points after transplantation, as well as our inability to monitor the immunologic threshold of risk versus safety in each individual patient. Recent advances in immunology/transplantation biology with the ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5381733 Thu, 27 Oct 2011 04:00:00 +0100 5381733 http://www.medworm.com/index.php?rid=5381734&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22000024%26dopt%3DAbstract Authors: Möröy T, Saba I, Kosan C Abstract The Myc interacting zinc finger protein 1 (Miz-1) is a BTB/POZ domain containing transcription factor that can function as an activator or repressor depending on its binding partners. In a complex with co-factors such as nuclophosmin or p300, Miz-1 stimulates transcription of genes that encode regulators of cell cycle progression such as p21(Cip1) or p15(Ink4b) or inhibitors of apoptosis such as Bcl-2. In contrast, Miz-1 becomes a transcriptional repressor when it binds to c-Myc or Bcl-6, which replace nucleophosmin or p300. During lymphocyte development, Miz-1 functions as a regulator of the IL-7 signaling pathway at very early steps in the bone marrow and thymus. When the IL-7 receptor (IL-7R) recognizes its cognate cytokine, a cascade... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5381734 Wed, 12 Oct 2011 04:00:00 +0100 5381734 http://www.medworm.com/index.php?rid=5313433&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21981947%26dopt%3DAbstract Authors: Thompson PK, Zúñiga-Pflücker JC Abstract The thymus is seeded by bone marrow-derived progenitors, which undergo a series of differentiation and proliferation events in order to generate functional T lymphocytes. The Notch signaling pathway, together with multiple transcription factors, act in concert to commit progenitors to a T-lineage fate, extinguishing non-T cell potential, inducing thymocyte differentiation and supporting proliferation and survival along the way to becoming a mature T cell. This review focuses on recent evidence regarding the complex interplay between the Notch pathway and other key transcription factors at specific lineage-decision points during the program of T cell development. PMID: 21981947 [PubMed - as supplied by publisher] (Source: Semi... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5313433 Thu, 06 Oct 2011 04:00:00 +0100 5313433 http://www.medworm.com/index.php?rid=5298471&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21978627%26dopt%3DAbstract Authors: Parsons RF, Redfield RR, Rodriguez E, Mustafa MM, Vivek K, Murayama M, Naji A, Noorchashm H Abstract The current mainstay of immunotherapy in clinical transplantation is T lymphocyte directed. However, it has long been appreciated that the emergence of an alloimmune response mounted by the B lymphocyte compartment and detectable as donor-specific antibodies is a critical challenge to long-term graft survival. Thus, achieving robust transplantation tolerance will require induction of tolerance in both the T- and B-cell compartments. Here we propose that the natural developmental propensity of the B-lymphocyte compartment acquisition of tolerance to self-antigens can be recapitulated to achieve humoral transplantation tolerance. It is our contention B-lymphocyte directed ind... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5298471 Tue, 04 Oct 2011 04:00:00 +0100 5298471 http://www.medworm.com/index.php?rid=5281831&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21963088%26dopt%3DAbstract Authors: Wang L, Xiong Y, Bosselut R Abstract The divergence of the two αβ T cell subsets defined by the mutually exclusive expression of CD4 and CD8 glycoproteins is an important event during the intrathymic differentiation of T lymphocytes. This reviews briefly summarizes the mechanisms that promote commitment to the CD4 or CD8 lineage in the thymus, and discusses the transcription factor circuits and epigenetic mechanisms that concur to maintain lineage integrity in post-thymic cells and yet allow effector cell differentiation. PMID: 21963088 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5281831 Wed, 28 Sep 2011 04:00:00 +0100 5281831 http://www.medworm.com/index.php?rid=5281833&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21958959%26dopt%3DAbstract Authors: Adams AB, Newell KA Abstract The rarity of tolerance following clinical transplantation has complicated the study of the responsible mechanisms. Several recent studies of kidney transplant recipients have demonstrated an association between increased numbers of B cells with less mature, inhibitory phenotypes and a state of tolerance. While a growing body of evidence from experimental models supports a role for B cells in regulating or suppressing immune responses, a causative role for B cells in clinical transplantation tolerance has yet to be proven. If B cells are conclusively shown to participate in the development of transplantation tolerance, it will be important to define the responsible mechanisms in order to design monitoring assays and immunosuppressive regimens t... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5281833 Tue, 27 Sep 2011 04:00:00 +0100 5281833 http://www.medworm.com/index.php?rid=5281832&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21958960%26dopt%3DAbstract Authors: Montgomery RA, Cozzi E, West LJ, Warren DS Abstract The humoral arm of the immune system provides robust protection against extracellular pathogens via the production of antibody molecules that neutralize or facilitate the destruction of microorganisms. However, the humoral immune system also provides a significant barrier to solid organ transplantation due to the antibody-mediated recognition of non-self proteins and carbohydrates expressed on transplanted organs. Historically, the presence of donor-specific antibodies (DSA) that recognize donor HLA molecules, incompatible ABO blood group antigens and other endothelial or xenogeneic antigens was considered a contraindication to transplantation. However, recent advances in antibody testing and immunosuppressive therapies h... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5281832 Tue, 27 Sep 2011 04:00:00 +0100 5281832 http://www.medworm.com/index.php?rid=5281834&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21944938%26dopt%3DAbstract Authors: Welinder E, Ahsberg J, Sigvardsson M Abstract Even though B-lymphocyte development is one of the best understood models for cell differentiation in the hematopoetic system, recent advances in cell sorting and functional genomics has increased this understanding further. This has suggested that already early lymphoid primed multipotent progenitor cells (LMPPs) express low levels of lymphoid restricted transcripts. The expression of these genes becomes more pronounced when cells enter the FLT-3/IL-7 receptor positive common lymphoid progenitor (CLP) stage. However, the expression of B-lineage specific genes is limited to a B-cell restricted Ly6D surface positive subpopulation of the CLP compartment. The gene expression patterns also reflect differences in lineage potential a... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5281834 Thu, 22 Sep 2011 04:00:00 +0100 5281834 http://www.medworm.com/index.php?rid=5281835&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21943504%26dopt%3DAbstract Authors: Sykes M, Levy G PMID: 21943504 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5281835 Wed, 21 Sep 2011 04:00:00 +0100 5281835 http://www.medworm.com/index.php?rid=5281836&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21940179%26dopt%3DAbstract Authors: Levine MH, Abt PL Abstract Antibody mediated rejection is a significant clinical problem encountered in a subset of renal transplant recipients. This type of rejection has a variable pathogenesis from the presence of donor specific antibodies with no overt disease to immediate hyperacute rejection and many variations between. Antibody mediated rejection is more common in human leukocyte antigen sensitized patients. In general, transplant graft survival after antibody mediated rejection is jeopardized, with less than 50% graft survival 5 years after this diagnosis. A variety of agents have been utilized singly and in combinations to treat antibody mediated rejection with differing results and significant research efforts are being placed on developing new targets for interv... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5281836 Tue, 20 Sep 2011 04:00:00 +0100 5281836 http://www.medworm.com/index.php?rid=5247637&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21937237%26dopt%3DAbstract Authors: Sarrazin S, Sieweke M Abstract In the predominant model of hematopoietic stem cell differentiation lineage commitment is thought to be initiated by stochastic variation in the balance of lineage determining transcription factors, whereas cytokines have been seen in a purely permissive role of stimulating selective survival and proliferation of the down stream progeny. Recent observations, however, indicate that cytokines can also directly instruct cell fate change in uncommitted stem and progenitor cells by activating lineage determining transcription factors. We review the historic and recent evidence for instructive cytokine signaling and propose a model that integrates cytokine signaling and transcription factor activity in the initial decision making process, where the... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5247637 Mon, 19 Sep 2011 04:00:00 +0100 5247637 http://www.medworm.com/index.php?rid=5247636&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21937238%26dopt%3DAbstract Authors: Baldwin WM, Halushka MK, Valujskikh A, Fairchild RL Abstract After many years of debate, there is now general agreement that B cells can participate in the immune response to cardiac transplants. Acute antibody-mediated rejection (AMR) is the best defined manifestation of B cell responses, but diagnostic and mechanistic questions still surround AMR. Many complement dependent mechanisms of antibody-mediated injury have been elucidated. C5 has become a therapeutic target that may not just truncate complement activation, but also may tip the balance away from inflammation by altering macrophage function. Additional complement independent effects have been identified. These may escape diagnosis and progress to chronic graft injury. The function of B cell infiltrates in cardiac... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5247636 Mon, 19 Sep 2011 04:00:00 +0100 5247636 http://www.medworm.com/index.php?rid=5247638&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21930392%26dopt%3DAbstract Authors: Mercer EM, Lin YC, Murre C Abstract Multiple trajectories have recently been described through which hematopoietic progenitor cells travel prior to becoming lineage-committed effectors. A wide spectrum of transcription factors has recently been identified that modulate developmental progression along such trajectories. Here we describe how distinct families of transcription factors act and are linked together to orchestrate early hematopoiesis. PMID: 21930392 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5247638 Sat, 17 Sep 2011 04:00:00 +0100 5247638 http://www.medworm.com/index.php?rid=5247640&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925896%26dopt%3DAbstract Authors: Cowan ML, Sciammas R, Chong AS Abstract The use of conventional immunosuppression has successfully improved short-term allograft survival, however, long-term allograft survival has remained static and is complicated by serious side effects secondary to the long-term use of immunosuppressive agents. Immunological tolerance is the ultimate goal of organ transplantation, however it is an infrequent event in humans. Accordingly, over the past several decades, there has been a push to fully understand both the cellular and molecular mechanisms that play a role in the induction and maintenance of tolerance, with recent data implicating B cells and donor specific alloantibody as a barrier to and potential mediator of allograft tolerance. The study of B cells and alloantibody in t... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5247640 Fri, 16 Sep 2011 04:00:00 +0100 5247640 http://www.medworm.com/index.php?rid=5247639&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925897%26dopt%3DAbstract Authors: Wilkes DS Abstract Lung transplantation is considered a definitive treatment for many lung diseases. However, rejection and other pathologic entities are major causes of morbidity and mortality for lung transplant recipients. Primary graft dysfunction (PGD) and obliterative bronchiolitis (OB) are the leading causes of early and late mortality, respectively. While the immune basis of PGD has not been clearly defined, evidence is emerging about roles for autoantibodies in this process. Similarly, the pathogenesis of OB has been linked recently to autoimmunity. This review will highlight the current understanding of autoantibodies in PGD and OB post lung transplantation. PMID: 21925897 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5247639 Fri, 16 Sep 2011 04:00:00 +0100 5247639 http://www.medworm.com/index.php?rid=5247642&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924923%26dopt%3DAbstract Authors: Nutt SL, Taubenheim N, Hasbold J, Corcoran LM, Hodgkin PD Abstract Upon activation by antigen, mature B cells undergo immunoglobulin class switch recombination and differentiate into antibody-secreting plasma cells, the endpoint of the B cell developmental lineage. Careful quantitation of these processes, which are stochastic, independent and strongly linked to the division history of the cell, has revealed that populations of B cells behave in a highly predictable manner. Considerable progress has also been made in the last few years in understanding the gene regulatory network that controls the B cell to plasma cell transition. The mutually exclusive transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription fa... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5247642 Thu, 15 Sep 2011 04:00:00 +0100 5247642 http://www.medworm.com/index.php?rid=5247641&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924924%26dopt%3DAbstract Authors: Satpathy AT, Murphy KM, K C W Abstract Dendritic cells (DCs) are a heterogeneous population within the mononuclear phagocyte system (MPS) that derive from bone marrow precursors. Commitment and specification of hematopoietic progenitors to the DC lineage is critical for the proper induction of both immunity and tolerance. This review summarizes the important cytokines and transcription factors required for differentiation of the DC lineage as well as further diversification into specific DC subsets. We highlight recent advances in the characterization of immediate DC precursors arising from the common myeloid progenitor (CMP). Particular emphasis is placed on the corresponding temporal expression of relevant factors involved in regulating developmental options. PMID: 2... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5247641 Thu, 15 Sep 2011 04:00:00 +0100 5247641 http://www.medworm.com/index.php?rid=5233312&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920772%26dopt%3DAbstract Authors: Fan H, Cao P, Game DS, Dazzi F, Liu Z, Jiang S Abstract The pursuit of transplantation tolerance is the holygrail in clinical organ transplantation. It has been established that regulatory T cells (Tregs) can confer donor-specific tolerance in mouse models of transplantation. However, this is crucially dependent on the strain combination, the organ transplanted and most importantly, the ratio of Tregs to alloreactive effector T cells. The ex vivo expansion of Tregs is one solution to increase the number of alloantigen specific cells capable of suppressing the alloresponse. Indeed, ex vivo expanded, alloantigen specific murine Tregs are shown to preferentially migrate to, and proliferate in, the graft and draining lymph node. In human transplantation it has been proposed th... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5233312 Tue, 13 Sep 2011 04:00:00 +0100 5233312 http://www.medworm.com/index.php?rid=5233311&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920773%26dopt%3DAbstract Authors: Möröy T, Khandanpour C Abstract T- and B-lymphocytes are important elements in the immune defense repertoire of higher organisms. The development and function of lymphoid cells is regulated at many levels one being the control of gene expression by transcription factors. The zinc finger transcriptional repressor Gfi1 has emerged as a factor that is critically implicated in the commitment of precursor cells for the lymphoid lineage. In addition, Gfi1 controls distinct stages of early T- or B-lymphoid development and is also critical for their maturation, activation and effector function. From many years of work, a picture emerges in which Gfi1 is part of a complicated, but well orchestrated network of interdependent regulators, most of which impinge on lymphoid developmen... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5233311 Tue, 13 Sep 2011 04:00:00 +0100 5233311 http://www.medworm.com/index.php?rid=5219478&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893418%26dopt%3DAbstract Authors: Pot C, Apetoh L, Awasthi A, Kuchroo VK Abstract Accumulating evidence indicates that IL-27, a member of the IL-12 family of cytokines, alleviates the severity of autoimmune diseases in both mice and men. The IL-27-induced activation of signal transducer and activator of transcription (Stat)1 and Stat3 promotes the generation of IL-10- producing type 1 regulatory T (Tr1) cells that inhibit effector T cells. In addition, IL-27 also suppresses the development of pathogenic IL-17-producing CD4(+) T cells (T(H)17) cells suggesting that pharmacological manipulations of IL-27 signaling pathway could be exploited therapeutically in regulating tissue inflammation. Here, we review how IL-27 controls inflammation through the regulation of Tr1 and T(H)17 responses. PMID: 21893418 ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5219478 Sat, 03 Sep 2011 04:00:00 +0100 5219478 http://www.medworm.com/index.php?rid=5194284&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21880506%26dopt%3DAbstract Authors: Wright GP, Stauss HJ, Ehrenstein MR Abstract There is accumulating evidence for regulatory T cell defects in rheumatoid arthritis and that some biologic interventions, in particular anti-TNF, can target this population. Despite the challenges in defining regulatory T cells in patients, there are a number of approaches currently being developed to utilise their potent immunosuppressive properties. Through genetic manipulation Tregs can be generated ex vivo or in vivo that target antigens present in the inflamed joint. Here we discuss these approaches, their refinement to restore tolerance in patients with rheumatoid arthritis, and strategies to prevent their conversion towards a Th17 phenotype. PMID: 21880506 [PubMed - as supplied by publisher] (Source: Seminars in Immu... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5194284 Sun, 28 Aug 2011 23:00:00 +0100 5194284 http://www.medworm.com/index.php?rid=5157607&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856168%26dopt%3DAbstract Authors: Hanidziar D, Koulmanda M Abstract As a consequence of ischemia-reperfusion injury of whole organ transplants and hypoxia-anoxia of cell transplants, transplantation unavoidably triggers adverse, cytodestructive inflammation within the allograft. Interventions that dampen adverse inflammation may limit the extent and duration of this injury, and preserve tissue function. Moreover, these interventions should create a milieu that guides many donor-activated T cells into a tissue-protective phenotype, thus promoting graft acceptance or even tolerance. Hence, it is useful, maybe crucial, to identify the measures that minimize deleterious consequences of acute and chronic inflammation upon allograft. Several therapies that inhibit activity of certain proinflammatory cytokines or... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5157607 Tue, 16 Aug 2011 23:00:00 +0100 5157607 http://www.medworm.com/index.php?rid=5157606&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856169%26dopt%3DAbstract Authors: Wojciechowski D, Vincenti F Abstract Signaling through the costimulatory pathway is critical in the regulation of T cell activation. Abatacept, a selective costimulatory antagonist FDA approved for the treatment of moderate to severe rheumatoid arthritis, binds to CD80 and CD86 on antigen presenting cells, blocking the interaction with CD28 on T cells. Belatacept, a second generation CTLA4-Ig with 2 amino acid substitutions, has shown considerable promise in clinical transplantation as part of a maintenance immunosuppression regimen. This review will summarize the role of costimulation in T cell activation, detail the development of costimulation antagonists and highlight the pertinent clinical trials completed and ongoing utilizing belatacept as part of an immunosuppressi... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5157606 Tue, 16 Aug 2011 23:00:00 +0100 5157606 http://www.medworm.com/index.php?rid=5157609&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21852150%26dopt%3DAbstract Authors: Bach JF, Chatenoud L PMID: 21852150 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5157609 Mon, 15 Aug 2011 23:00:00 +0100 5157609 http://www.medworm.com/index.php?rid=5157608&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21852151%26dopt%3DAbstract Authors: Michels AW, Eisenbarth GS Abstract Type 1 diabetes (T1D) is a chronic autoimmune disease that results in the specific immune destruction of insulin producing beta cells. Currently there is no cure for T1D and treatment for the disease consists of lifelong administration of insulin. Immunotherapies aimed at preventing beta cell destruction in T1D patients with residual c-peptide or in individuals developing T1D are being evaluated. Networks of researchers such as TrialNet and the Immune Tolerance Network in the U.S. and similar networks in Europe have been established to evaluate such immunotherapies. This review focuses on immune intervention for the prevention and amelioration of human T1D with a focus on potential immune suppressive, antigen specific and environmental th... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5157608 Mon, 15 Aug 2011 23:00:00 +0100 5157608 http://www.medworm.com/index.php?rid=5141816&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21846589%26dopt%3DAbstract Authors: Bach JF, Chatenoud L Abstract Type 1 diabetes is an autoimmune disease. It was thus logical to attempt preventing or stopping the progression of the disease by immunotherapy. Following the strategies used in organ transplantation, the first trials in the 80s used cyclosporin in patients presenting recently diagnosed Type 1 diabetes. The effect was spectacular but waned when the treatment was stopped as the effect was non antigen-specific. Going back from bed to bench-side major efforts were then devoted to device strategies allowing induction or restoration of self-tolerance. Two major approaches provided encouraging results when used in spontaneous models of autoimmune diabetes that are the use of β-cell autoantigens and of monoclonal antibodies to CD3. Based on these re... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5141816 Sat, 13 Aug 2011 23:00:00 +0100 5141816 http://www.medworm.com/index.php?rid=5141817&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840222%26dopt%3DAbstract Authors: Pot C, Apetoh L, Kuchroo VK Abstract The ability of IL-10 producing Type 1 regulatory T cells (Tr1) to restrain the activation of effector immune cells during autoimmune responses underscores their essential role in maintaining immune tolerance. While mouse studies have demonstrated that increasing the numbers and/or function of Tr1 cells could improve the course of autoimmune diseases, the inability to generate Tr1 cells in vitro in large numbers has hampered identification of the molecular mechanisms responsible for their differentiation. Interleukin-27 (IL-27), a member of the IL-12 heterodimeric cytokine family, was identified as an important cytokine that suppresses effector T(H)17 cells and promotes the generation of Tr1 cells. Tr1 cells dampen autoimmunity and tissu... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5141817 Wed, 10 Aug 2011 23:00:00 +0100 5141817 http://www.medworm.com/index.php?rid=5141818&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839648%26dopt%3DAbstract Authors: Sachs DH, Sykes M, Kawai T, Cosimi AB Abstract The induction of transplantation tolerance could liberate organ transplant recipients from the complications of life-long chronic immunosuppression. The original description of tolerance induction through mixed hematopoietic chimerism in mice utilized lethal whole body irradiation as the preparative regimen for achieving mixed chimerism. While such a regimen might be acceptable for treatment of patients with malignancies, which might also respond to the therapeutic effects of radiation, its toxicity would be unacceptable for patients in need only of an organ transplant. Graft-vs.-host disease, which is frequently a complication of mismatched bone marrow transplantation, would likewise be unacceptable for ordinary clinical tran... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5141818 Tue, 09 Aug 2011 23:00:00 +0100 5141818 http://www.medworm.com/index.php?rid=5141819&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21831659%26dopt%3DAbstract Authors: Battaglia M, Roncarolo MG Abstract In type 1 diabetes (T1D), insulin-producing pancreatic β-cells are attacked and destroyed by the immune system. Although man-made insulin is life-saving, it is not a cure and it cannot prevent long-term complications. In addition, most T1D patients would do almost anything to achieve release from the burden of daily glucose monitoring and insulin injection. Despite the formation of very large and promising clinical trials, a means to prevent/cure T1D in humans remains elusive. This has led to an increasing interest in the possibility of using T cells with regulatory properties (Treg cells) as a biological therapy to preserve and restore tolerance to self-antigens. In the present review we will attempt to consolidate learning from the pas... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5141819 Sun, 07 Aug 2011 23:00:00 +0100 5141819 http://www.medworm.com/index.php?rid=5141820&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820917%26dopt%3DAbstract Authors: Hippen KL, Riley JL, June CH, Blazar BR Abstract Three main types of CD4+ regulatory T cells can be distinguished based upon whether they express Foxp3 and differentiate naturally in the thymus (natural Tregs) or are induced in the periphery (inducible Tregs); or whether they are FoxP3 negative but secrete IL-10 in response to antigen (Tregulatory type 1, Tr1 cells). Adoptive transfer of each cell type has proven highly effective in mouse models at preventing graft vs. host disease (GVHD) and autoimmunity. Although clinical application was initially hampered by low Treg frequency and unfavorable ex vivo expansion properties, several phase I trials are now being conducted to assess their effect on GVHD following hematopoietic stem cell transplantation (HSCT) and in type I d... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5141820 Wed, 03 Aug 2011 23:00:00 +0100 5141820 http://www.medworm.com/index.php?rid=5058530&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752667%26dopt%3DAbstract Authors: Maruyama T, Konkel JE, Zamarron BF, Chen W Induction of Foxp3 gene expression and acquisition of regulatory T cell fate is, understandably, a highly controlled process and one which many investigators want to illuminate. In studying the regulation of Foxp3 gene expression, several conserved non-coding regions have been identified and the role of various transcription factors at these sites has been explored. What emerges is that many factors, some positive, some negative, interact to collectively drive Foxp3 gene expression and then maintain its expression in Foxp3(+) regulatory T cells. TCR signaling is imperative for Foxp3 gene expression and TGF-β is a key cytokine for initiating Foxp3 gene expression in naïve T cells. But other signaling pathways are also known to play a... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5058530 Sun, 10 Jul 2011 23:00:00 +0100 5058530 http://www.medworm.com/index.php?rid=5058531&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741270%26dopt%3DAbstract Authors: Ezzelarab M, Thomson AW The pursuit of clinical transplant tolerance has led to enhanced understanding of mechanisms underlying immune regulation, including the characterization of immune regulatory cells, in particular antigen-presenting cells (APC) and regulatory T cells (Treg), that may play key roles in promoting operational tolerance. Dendritic cells (DC) are highly efficient APC that have been studied extensively in rodents and humans, and more recently in non-human primates. Owing to their ability to regulate both innate and adaptive immune responses, DC are considered to play crucial roles in directing the alloimmune response towards transplant tolerance or rejection. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, the in... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5058531 Tue, 05 Jul 2011 23:00:00 +0100 5058531 http://www.medworm.com/index.php?rid=5011205&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21733719%26dopt%3DAbstract Authors: Klein L, Jovanovic K A substantial fraction of the Foxp3(+) CD4(+) regulatory T (T(reg)) cell repertoire is generated through instructive and/or selective processes in the thymus, and there is some consensus that clonal deviation into the T(reg) lineage is a result of self-antigen recognition. Paradoxically, the same holds true for a diametrically different cell fate decision of developing thymocytes, namely their removal from the repertoire through apoptotic cell death (clonal deletion). Here, we will review our current understanding of how T cell receptor stimulation, cytokine signaling, co-stimulation, epigenetic modifications and T cell intrinsic developmental tuning synergize during T(reg) cell differentiation, and how instructive signals converge at the Foxp3 gene-locus ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5011205 Sun, 03 Jul 2011 23:00:00 +0100 5011205 http://www.medworm.com/index.php?rid=5011207&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724410%26dopt%3DAbstract Authors: Cipolletta D, Kolodin D, Benoist C, Mathis D Foxp3+CD4+ regulatory T (T(reg)) cells are a key population in controlling the immune response. Recently, their roles have been expanded to broader, non-immune, contexts, in particular the metabolic consequences downstream of obesity-induced inflammation, e.g. type-2 diabetes and cardiovascular disease. This review highlights the major innate and adaptive immune cell subsets contributing to adipose-tissue inflammation, the key role played by fat-resident T(regs), and the potential of T(reg)-based therapies for treatment of the metabolic syndrome. PMID: 21724410 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5011207 Thu, 30 Jun 2011 23:00:00 +0100 5011207 http://www.medworm.com/index.php?rid=5011206&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724411%26dopt%3DAbstract Authors: Daniel C, von Boehmer H Fopx3(+) Treg safeguard against autoimmune diseases and immune pathology. The extrathymic conversion of naïve T cells into Foxp3(+) regulatory T cells can be achieved in vivo by the delivery of strong-agonist ligands under subimmunogenic conditions. Tolerogenic vaccination with strong-agonist mimetopes of self-antigen to promote self-antigen specific tolerance may represent the most specific and safest means of preventing autoimmunity. This review discusses the requirements for induction of dominant tolerance exerted by Foxp3(+) Tregs in autoimmunity with special emphasis on their impact to interfere with T1D. The future goals are the understanding of self-non-self discrimination at the cellular and molecular level, which should then enable investigato... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5011206 Thu, 30 Jun 2011 23:00:00 +0100 5011206 http://www.medworm.com/index.php?rid=5011208&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723740%26dopt%3DAbstract Authors: Oberbarnscheidt MH, Zecher D, Lakkis FG The vertebrate innate immune system consists of inflammatory cells and soluble mediators that comprise the first line of defense against microbial infection and, importantly, trigger antigen-specific T and B cell responses that lead to lasting immunity. The molecular mechanisms responsible for microbial non-self recognition by the innate immune system have been elucidated for a large number of pathogens. How the innate immune system recognizes non-microbial non-self, such as organ transplants, is less clear. In this review, we approach this question by describing the principal mechanisms of non-self, or 'damaged' self, recognition by the innate immune system (pattern recognition receptors, the missing self theory, and the danger hypothes... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5011208 Wed, 29 Jun 2011 23:00:00 +0100 5011208 http://www.medworm.com/index.php?rid=5011209&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21705229%26dopt%3DAbstract Authors: Strober S, Spitzer TR, Lowsky R, Sykes M Allogeneic hematopoietic cell transplantation (HCT) has most commonly been used to treat hematologic malignancies, where it is often the only potentially curative option available. The success of HCT has been limited by transplant-associated toxicities related to the conditioning regimens used and to the common immunologic consequence of donor T cell recognition of recipient alloantigens, graft-vs-host disease (GVHD). The frequency and severity of GVHD observed when extensive HLA barriers are transgressed has essentially precluded the routine use of extensively HLA-mismatched HCT. Allogeneic HCT also has potential as an approach to organ allograft tolerance induction, but this potential has not been previously realized because of the to... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=5011209 Thu, 23 Jun 2011 23:00:00 +0100 5011209 http://www.medworm.com/index.php?rid=4918529&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21616680%26dopt%3DAbstract Authors: Pilat N, Sayegh MH, Wekerle T Secondary, so-called costimulatory, signals are critically required for the process of T cell activation. Since landmark studies defined that T cells receiving a T cell receptor signal without a costimulatory signal, are tolerized in vitro, the investigation of T cell costimulation has attracted intense interest. Early studies demonstrated that interrupting T cell costimulation allows attenuation of the alloresponse, which is particularly difficult to modulate due to the clone size of alloreactive T cells. The understanding of costimulation has since evolved substantially and now encompasses not only positive signals involved in T cell activation but also negative signals inhibiting T cell activation and promoting T cell tolerance. Costimulation b... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4918529 Tue, 24 May 2011 23:00:00 +0100 4918529 http://www.medworm.com/index.php?rid=4918528&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21620722%26dopt%3DAbstract Authors: McMurchy AN, Bushell A, Levings MK, Wood KJ Decreasing the incidence of chronic rejection and reducing the need for life-long immunosuppression remain important goals in clinical transplantation. In this article, we will review how regulatory T cells (Treg) came to be recognized as an attractive way to prevent or treat allograft rejection, the ways in which Treg can be manipulated or expanded in vivo, and the potential of in vitro expanded/generated Treg for cellular therapy. We will describe the first regulatory T cell therapies that have been or are in the process of being conducted in the clinic as well as the safety concerns of such therapies and how outcomes may be measured. PMID: 21620722 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4918528 Tue, 24 May 2011 23:00:00 +0100 4918528 http://www.medworm.com/index.php?rid=4869238&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592823%26dopt%3DAbstract Authors: Shalev I, Schmelzle M, Robson SC, Levy G Several types of regulatory T cells maintain self-tolerance and control excessive immune responses to foreign antigens. The major regulatory T subsets described over the past decade and novel function in transplantation will be covered in this review with a focus on CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells. Multiple mechanisms have been proposed to explain how Treg cells inhibit effector cells but none can completely explain the observed effects in toto. Proposed mechanisms to explain suppressive activity of Treg cells include the generation of inhibitory cytokines, induced death of effector cells by cytokine deprivation or cytolysis, local metabolic perturbation of target cells mediated by changes in extracellular nucleotide/nuc... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4869238 Sun, 15 May 2011 23:00:00 +0100 4869238 http://www.medworm.com/index.php?rid=4592850&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21397517%26dopt%3DAbstract Authors: Wahren-Herlenius M, Kuchroo VK PMID: 21397517 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4592850 Thu, 10 Mar 2011 00:00:00 +0100 4592850 http://www.medworm.com/index.php?rid=4592851&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376627%26dopt%3DAbstract Authors: Klareskog L, Malmström V, Lundberg K, Padyukov L, Alfredsson L This review describes how studies on interactions between genetic variants, and environmental factors, mainly smoking, contribute to the understanding of how autoimmunity to post-translationally (citrullinated) proteins/peptides may occur and potentially contribute to certain subsets of rheumatoid arthritis. A main message is that studies on specific immune mechanisms in a complex and heterogeneous disease like RA should be undertaken with the help of results from genetic epidemiology. By those means, it may be possible to identify subsets of RA in a way that in the end allows development and testing of precise and subset-specific interventions against environment as well as genetically defined molecular pathways,... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4592851 Wed, 02 Mar 2011 00:00:00 +0100 4592851 http://www.medworm.com/index.php?rid=4478719&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21316261%26dopt%3DAbstract Authors: Hashimoto D, Merad M In clinical practice, hematopoietic cell transplantation (HCT) is now recognized as a powerful means of delivering effective cellular immunotherapy for malignant and non-malignant diseases. In patients with severe hematological malignancies, the success of allogeneic HCT is largely based on immunologic graft-versus-tumor (GVT) effects mediated by allogeneic T lymphocytes present in the graft. Unfortunately, this beneficial effect is counterbalanced by the occurrence of graft versus host reactions directed against normal host tissues resulting in graft versus host disease (GVHD), a potentially life-threatening complication that limits the success of allogeneic HCT. Therefore, while preserving beneficial GVT effects, a major objective in allogeneic HCT is th... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478719 Thu, 10 Feb 2011 00:00:00 +0100 4478719 http://www.medworm.com/index.php?rid=4478721&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21306912%26dopt%3DAbstract Authors: Wucherpfennig KW, Sethi D The major histocompatibility complex (MHC) on human chromosome 6 represents the most important genetic locus for a number of common human autoimmune diseases. Specific alleles that differ from closely related alleles by only one or a few amino acids in the peptide binding groove are frequently strongly associated with disease susceptibility, raising the important question of which peptide presentation events are critical in disease initiation and progression. This review will cover a number of topics pertinent to this fundamental question, including MHC linked disease susceptibility to autoimmune diseases, molecular mechanisms for the role of MHC molecules in autoimmune diseases as well as the recognition of self and microbial peptides by self-reactiv... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478721 Mon, 07 Feb 2011 00:00:00 +0100 4478721 http://www.medworm.com/index.php?rid=4478720&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21306913%26dopt%3DAbstract Authors: Green NM, Marshak-Rothstein A Studies over the past decade have demonstrated a key role for pattern recognition receptors in the activation of autoreactive B cells. Self reactive B cells that manage to escape negative selection often express relatively low affinity receptors for self antigens (ignorant B cells), and can only be activated by integrating a relatively weak BCR signal with signals from additional receptors. Members of the toll-like receptor (TLR) gene family, and especially the nucleic acid binding receptors TLR 7, 8 and 9, appear to play a key role in this regard and promote the production of autoantibodies reactive with DNA- or RNA-associated autoantigens. These autoantibodies are able to form immune complexes with soluble or cell-bound ligands, and these immune... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478720 Mon, 07 Feb 2011 00:00:00 +0100 4478720 http://www.medworm.com/index.php?rid=4478722&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21296592%26dopt%3DAbstract Authors: Zaccone P, Cooke A While some infectious agents have been linked to onset of autoimmune disease there is also other evidence suggesting that certain infectious agents might inhibit autoimmune pathology. This review focuses on the ways in which infectious agents or their products might intervene in an autoimmune response. PMID: 21296592 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478722 Fri, 04 Feb 2011 00:00:00 +0100 4478722 http://www.medworm.com/index.php?rid=4478747&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21295490%26dopt%3DAbstract Authors: Chu CC, Di Meglio P, Nestle FO The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478747 Wed, 02 Feb 2011 00:00:00 +0100 4478747 http://www.medworm.com/index.php?rid=4478742&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21295491%26dopt%3DAbstract Authors: Apetoh L, Locher C, Ghiringhelli F, Kroemer G, Zitvogel L Dendritic cells (DCs) are central to the initiation of tumor-specific immune responses. However, the tumor microenvironment generates immunosuppressive cells and soluble mediators that compromise DC functions and limit the success of DC-based therapies. Progress in understanding DC metabolism in cancer is uncovering novel therapeutic targets that could restore DC capacity to prime T cells and trigger effective anticancer responses. Accumulating evidence also indicates that conventional chemo- and radiotherapy protocols can cause DC activation, enhance antigen cross-presentation, selectively eliminate immunosuppressive cells and revert the immunosuppression state caused by cancer, suggesting that relevant chemoimmunother... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478742 Wed, 02 Feb 2011 00:00:00 +0100 4478742 http://www.medworm.com/index.php?rid=4478723&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21295492%26dopt%3DAbstract Authors: Hardenberg G, Steiner TS, Levings MK Inflammatory bowel disease (IBD) is characterized by chronic, idiopathic inflammation of the intestine. The disease is thought to result from a combination of genetic and environmental factors which ultimately leads to a mucosal immune system that overreacts to normal constituents of the mucosal microbiota. The inflammation in IBD is primarily mediated by inappropriate production of proinflammatory cytokines by CD4(+) T effector cells, effects that are suppressed by CD4(+) T regulatory cells. Defects in both the function of T regulatory cells, and the ability of T effector cells to be suppressed, have been implicated in IBD. In this review we will discuss environmental factors, including cytokines, vitamins A and D, and commensal bacteria, ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478723 Wed, 02 Feb 2011 00:00:00 +0100 4478723 http://www.medworm.com/index.php?rid=4478751&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292499%26dopt%3DAbstract Authors: Kranich J, Maslowski KM, Mackay CR The gut microbiota has recently been recognized for its role in immune regulation, and changes in gut microbiota may be the basis for an increased incidence of autoimmune diseases and asthma in developed countries. Beneficial microbes produce factors that are distributed systemically, and therefore can influence peripheral inflammatory responses. Such symbiosis factors are important for the control and resolution of inflammation and autoimmune diseases. Here we discuss immune regulation by recently identified symbiosis factors and how certain environmental factors favor their production and influence the composition of the gut microflora. PMID: 21292499 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478751 Tue, 01 Feb 2011 00:00:00 +0100 4478751 http://www.medworm.com/index.php?rid=4478750&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292500%26dopt%3DAbstract Authors: Atarashi K, Umesaki Y, Honda K The mammalian alimentary tract harbors hundreds of bacterial species that constitute the indigenous microbial flora. The indigenous microbial flora has long been appreciated for its role in host immune system development. Recent reports suggest that components of the microbial flora differentially affect the proportion and number of functionally distinct subsets of T cells in the intestine. Substantial changes in the composition of the microbiota are associated with inflammatory bowel disease. This review will discuss the importance of individual species of microbial flora in the induction of T cell subsets, particularly Th17 cells and regulatory T (Treg) cells in the intestine. PMID: 21292500 [PubMed - as supplied by publisher] (Source: Semi... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478750 Tue, 01 Feb 2011 00:00:00 +0100 4478750 http://www.medworm.com/index.php?rid=4478749&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292501%26dopt%3DAbstract Authors: Rönnblom L, Alm GV, Eloranta ML The type I interferon (IFN) system induces inhibition of viral replication, but can also activate the innate and adaptive immune system. An important role of the type I IFN system in autoimmune diseases, including lupus, is suggested by the observation that these disorders display a prominent over-expression of type I IFN regulated genes. The development of autoimmune diseases in some individuals treated with IFN-α directly supports a pivotal role for this cytokine in breaking tolerance and inducing autoimmune reactions. A genetic setup that promotes type I IFN production and/or response and the presence of endogenous inducers of IFN-α production have been described in patients with lupus. Several known environmental risk factors for developm... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478749 Tue, 01 Feb 2011 00:00:00 +0100 4478749 http://www.medworm.com/index.php?rid=4478748&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292502%26dopt%3DAbstract Authors: Bar-On L, Zigmond E, Jung S Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis represent a major challenge to clinicians and immunologists trying to understand why in certain individuals the peaceful coexistence of the commensal microflora and its host breaks down and results in chronic inflammation. Here we summarize the recent progress in our understanding of the organization of the intestinal mononuclear phagocytes with dendritic cells and macrophages of distinct phenotype, origin and function. Finally, we discuss potential strategies to translate the recent findings into the management of chronic inflammation in animal models of IBD. PMID: 21292502 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478748 Tue, 01 Feb 2011 00:00:00 +0100 4478748 http://www.medworm.com/index.php?rid=4478753&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288737%26dopt%3DAbstract Authors: Stockinger B, Hirota K, Duarte J, Veldhoen M The aryl hydrocarbon receptor (AhR), subject of intensive research over three decades by the pharmacology/toxicology field has recently made its entry into mainstream immunology research and is set to continue to intrigue with ever more complex modes of modulating immune responses. The discovery of high and selective AhR expression on Th17 cells [1-3] and its role in induction of the cytokine IL-22 [1] attributed new immunological functions to this transcription factor and stimulated further research into physiological functions of the AhR in the immune system. A number of recent reviews [4-11] have highlighted potential new avenues of research. This review addresses recent new insight into physiological roles of AhR in the immune s... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478753 Mon, 31 Jan 2011 00:00:00 +0100 4478753 http://www.medworm.com/index.php?rid=4478752&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288738%26dopt%3DAbstract Authors: Rai E, Wakeland EK Rapid advances in genetic technologies have led to the identification of more than 85 loci that contribute to susceptibility to autoimmune diseases. These susceptibility genes are distributed throughout the innate and adaptive immune systems, indicating that dysregulations in both immune systems participate in the development of autoimmunity. A significant subset of these susceptibility genes are shared between multiple autoimmune diseases. However, the dysregulation of specific pathways, such as the pathogen recognition receptors of the innate immune system and the TNF supergene family, are significantly involved in some autoimmune diseases. Although these findings dramatically increase the details available concerning the nature of genetic predisposition t... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478752 Mon, 31 Jan 2011 00:00:00 +0100 4478752 http://www.medworm.com/index.php?rid=4478754&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277223%26dopt%3DAbstract Authors: Ueno H, Klechevsky E, Schmitt N, Ni L, Flamar AL, Zurawski S, Zurawski G, Palucka K, Banchereau J, Oh S Dendritic cells (DCs) were discovered in 1973 by Ralph Steinman as a previously undefined cell type in the mouse spleen and are now recognized as a group of related cell populations that induce and regulate adaptive immune responses. Studies of the past decade show that, both in mice and humans, DCs are composed of subsets that differ in their localization, phenotype, and functions. These progresses in our understanding of DC biology provide a new framework for improving human health. In this review, we discuss human DC subsets in the context of their medical applications, with a particular focus on DC targeting. PMID: 21277223 [PubMed - as supplied by publisher] (Source... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4478754 Thu, 27 Jan 2011 00:00:00 +0100 4478754 http://www.medworm.com/index.php?rid=4413950&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21269839%26dopt%3DAbstract Authors: Tacken PJ, Figdor CG During the past decade, the immunotherapeutic potential of ex vivo generated professional antigen presenting dendritic cells (DCs) has been explored in the clinic. Albeit safe, clinical results have thus far been limited. A major disadvantage of current cell-based dendritic cell (DC) therapies, preventing universal implementation of this form of immunotherapy, is the requirement that vaccines need to be tailor made for each individual. Targeted delivery of antigens to DC surface receptors in vivo would circumvent this laborious and expensive ex vivo culturing steps involved with these cell-based therapies. In addition, the opportunity to target natural and often rare DC subsets in vivo might have advantages over loading more artificial ex vivo cultured DCs... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4413950 Mon, 24 Jan 2011 00:00:00 +0100 4413950 http://www.medworm.com/index.php?rid=4281583&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832333%26dopt%3DAbstract Authors: Bergman Y, Cedar H Immune receptor gene expression is regulated by a series of developmental events that modify their accessibility in a locus, cell type, stage and allele-specific manner. This is carried out by a programmed combination of many different molecular mechanisms, including region-wide replication timing, changes in nuclear localization, chromatin contraction, histone modification, nucleosome positioning and DNA methylation. These modalities ultimately work by controlling steric interactions between receptor loci and the recombination machinery. PMID: 20832333 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4281583 Wed, 01 Dec 2010 00:00:00 +0100 4281583 http://www.medworm.com/index.php?rid=4281582&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20833065%26dopt%3DAbstract Authors: Degner-Leisso SC, Feeney AJ V(D)J recombination is a crucial component of the adaptive immune response, allowing for the production of a diverse antigen receptor repertoire (Ig and TCR). This review will focus on how epigenetic regulation and 3-dimensional (3D) interactions may control V(D)J recombination at Ig loci. The interplay between transcription factors and post-translational modifications at the Igh, Igκ, and Igλ loci will be highlighted. Furthermore, we propose that the spatial organization and epigenetic boundaries of each Ig loci before and during V(D)J recombination may be influenced in part by the CTCF/cohesin complex. Taken together, the many epigenetic and 3D layers of control ensure that Ig loci are only rearranged at appropriate stages of B cell development.... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4281582 Wed, 01 Dec 2010 00:00:00 +0100 4281582 http://www.medworm.com/index.php?rid=4281581&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20863715%26dopt%3DAbstract Authors: Corcoran AE Within the lymphocyte lineages, restriction of immunoglobulin V(D)J recombination to B cells and T cell receptor (TCR) recombination to T cells is governed by a myriad of epigenetic mechanisms that control the chromatin accessibility of these loci to the Rag recombinase machinery in a lineage and developmental stage-specific manner. These mechanisms operate both locally at individual gene segments, and globally over large chromatin domains in these enormous multigene loci. In this review we will explore the established and emerging roles of three aspects of epigenetic regulation that contribute to large-scale control of the immunoglobulin heavy chain locus in B cells: non-coding RNA transcription, regulatory elements, and nuclear organization. Recent conceptual and... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4281581 Wed, 01 Dec 2010 00:00:00 +0100 4281581 http://www.medworm.com/index.php?rid=4281580&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20864355%26dopt%3DAbstract Authors: Subrahmanyam R, Sen R The immunoglobulin heavy chain (IgH) gene locus is activated at a precise stage of B lymphocyte development to undergo gene rearrangements that assemble the functional gene. In this review we summarize our current understanding of the chromatin state of the IgH as it appears just prior to the initiation of V(D)J recombination, and the implications of this structure for regulation of recombination. We also examine the role of the intron enhancer, Eμ, in establishing the pre-rearrangement chromatin structure. The emerging picture shows that the IgH locus consists of independently regulated domains, each of which requires multiple levels of epigenetic changes to reach the fully activated state. PMID: 20864355 [PubMed - indexed for MEDLINE] (Source: Semi... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4281580 Wed, 01 Dec 2010 00:00:00 +0100 4281580 http://www.medworm.com/index.php?rid=4140129&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21036059%26dopt%3DAbstract Authors: Desiderio S In developing lymphocytes, V(D)J recombination is subject to tight spatial and temporal regulation. An emerging body of evidence indicates that some of these constraints, particularly with respect to locus specificity and cell cycle phase, are enforced by regulatory cues that converge directly on the RAG proteins themselves. Active chromatin is bound by RAG-2 through a specific histone modification that may serve the recombinase as an allosteric activator as well as a docking site. RAG-1 possesses intrinsic histone ubiquitin ligase activity, suggesting that the recombinase not only responds to chromatin modification but is itself able to modify chromatin. The cyclin A/Cdk2 component of the cell cycle clock triggers periodic destruction of RAG-2, thereby restricting... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4140129 Thu, 28 Oct 2010 00:00:00 +0100 4140129 http://www.medworm.com/index.php?rid=4078343&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20952207%26dopt%3DAbstract Authors: Feeney A PMID: 20952207 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=4078343 Thu, 14 Oct 2010 23:00:00 +0100 4078343 http://www.medworm.com/index.php?rid=3958125&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20627765%26dopt%3DAbstract Authors: Sultana DA, Bell JJ, Zlotoff DA, De Obaldia ME, Bhandoola A Multipotent progenitors arrive at the thymus via the blood. Constraining the non-T cell fates of these progenitors while promoting the T cell fate is a major task of the thymus. Notch appears to be the initial trigger for a developmental program that eventually results in T cell lineage commitment. Several downstream targets of Notch are known, but the specific roles of each are poorly understood. A greater understanding of how Notch and other thymic signals direct progenitors to a T cell fate could be useful for translational work. For example, such work could eventually allow for the generation of fully competent T cells in vitro that could supplement the waning T cell numbers and function in the elderly and boost T... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3958125 Sat, 11 Sep 2010 10:30:35 +0100 3958125 http://www.medworm.com/index.php?rid=3958124&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20827529%26dopt%3DAbstract Authors: Thomas MF, Ansel KM Since the phenomenon of small RNA-mediated gene silencing was first described over 15 years ago (Lee et al. Cell 75:843-854, 1993; Wightman et al. Cell 75:855-862, 1993), it has become evident that a variety of endogenous small RNAs play an important role in establishing and maintaining cell lineages. MicroRNAs (miRNAs), in particular, have been shown to exert regulatory control over the development and function of the many specialized cells that comprise the mammalian immune system (Baltimore et al. Nat Immunol 9:839-845, 2008; Kanellopoulous and Monticelli Semin Cancer Biol 18:79-88, 2008; Xiao and Rajewsky Cell 136:26-36, 2009). The advent of next generation sequencers provides an important tool for profiling the small RNA transcriptome of many diverse c... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3958124 Sat, 11 Sep 2010 10:30:07 +0100 3958124 http://www.medworm.com/index.php?rid=3958123&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20829065%26dopt%3DAbstract This article describes our current knowledge of how genetic elements orchestrate crosstalk with epigenetic mechanisms to regulate recombinase accessibility via localized, regional, or long-range changes in chromatin. PMID: 20829065 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3958123 Mon, 06 Sep 2010 23:00:00 +0100 3958123 http://www.medworm.com/index.php?rid=3958122&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20829066%26dopt%3DAbstract Authors: Spicuglia S, Pekowska A, Zacarias-Cabeza J, Ferrier P V(D)J recombination assembles antigen receptor genes from germline V, D and J segments during lymphocyte development. In αβT-cells, this leads to the subsequent expression of T-cell receptor (TCR) β and α chains. Generally, V(D)J recombination is closely controlled at various levels, including cell-type and cell-stage specificities, order of locus/gene segment recombination, and allele usage to mediate allelic exclusion. Many of these controls rely on the modulation of gene accessibility to the recombination machinery, involving not only biochemical changes in chromatin arrangement and structural modifications of chromosomal organization and positioning, but also the refined composition of the recombinase target... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3958122 Mon, 06 Sep 2010 23:00:00 +0100 3958122 http://www.medworm.com/index.php?rid=3934911&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20810991%26dopt%3DAbstract Authors: Tawara I, Shlomchik WD, Jones A, Zou W, Nieves E, Liu C, Toubai T, Duran-Struuck R, Sun Y, Clouthier SG, Evers R, Lowler KP, Levy RB, Reddy P Allogeneic bone marrow transplantation is an effective treatment for a number of malignant and nonmalignant diseases (Applebaum. 2001. Nature. 411: 385-389 and Copelan. 2006. N Engl J Med. 354: 1813-1826). However, the application of this therapeutic modality has been impeded by a number of confounding side effects, the most frequent and severe of which is the development of graft-versus-host disease (GVHD) (Copelan. 2006. N Engl J Med. 354: 1813-1826 and Blazar and Murphy. 2005. Philos Trans R Soc Lond B Biol Sci. 360: 1747-1767). Alloreactive donor T cells are critical for causing GVHD (Fowler. 2006. Crit Rev Oncol Hematol. 57: 225-244... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3934911 Tue, 31 Aug 2010 23:00:00 +0100 3934911 http://www.medworm.com/index.php?rid=3795675&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655758%26dopt%3DAbstract Authors: Singer A PMID: 20655758 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3795675 Wed, 21 Jul 2010 23:00:00 +0100 3795675 http://www.medworm.com/index.php?rid=3761892&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20630771%26dopt%3DAbstract Authors: Vicente R, Swainson L, Marty-Grès S, De Barros SC, Kinet S, Zimmermann VS, Taylor N The thymus forms as an alymphoid thymic primordium with T cell differentiation requiring the seeding of this anlage. This review will focus on the characteristics of the hematopoietic progenitors which colonize the thymus and their subsequent commitment/differentiation, both in mice and men. Within the thymus, the interplay between Notch1 and IL-7 signals is crucial for the orchestration of T cell development, but the precise requirements for these factors in murine and human thympoeisis are not synonymous. Recent advances in our understanding of the mechanisms regulating precursor entry and their maintenance in the thymus will also be presented. PMID: 20630771 [PubMed - as supplied by p... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3761892 Sun, 11 Jul 2010 23:00:00 +0100 3761892 http://www.medworm.com/index.php?rid=3761891&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20630772%26dopt%3DAbstract Authors: Yashiro-Ohtani Y, Ohtani T, Pear WS Notch signaling plays multiple roles in T cell development. Following thymic entry, Notch signals are required to specify the T cell fate from a multipotent hematopoietic progenitor. At subsequent steps in early T cell development, Notch provides important differentiation, survival, proliferation and metabolic signals. This review focuses on the multiple functions of Notch in early T cell development, from T cell specification in the thymus through beta selection. PMID: 20630772 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3761891 Sun, 11 Jul 2010 23:00:00 +0100 3761891 http://www.medworm.com/index.php?rid=3693977&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20570531%26dopt%3DAbstract Authors: Finn OO, Banchereau J PMID: 20570531 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3693977 Thu, 03 Jun 2010 23:00:00 +0100 3693977 http://www.medworm.com/index.php?rid=3684040&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20552730%26dopt%3DAbstract Authors: Finn OO, Banchereau J PMID: 20552730 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3684040 Mon, 31 May 2010 23:00:00 +0100 3684040 http://www.medworm.com/index.php?rid=3663256&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20537908%26dopt%3DAbstract Authors: O'Reilly RJ, Dao T, Koehne G, Scheinberg D, Doubrovina E Adoptive transfer of in vivo generated antigen-specific donor-derived T-cells is increasingly recognized as an effective approach for the treatment or prevention of EBV lymphomas and cytomegalovirus infections complicating allogeneic hematopoietic cell transplants. This review examines evidence from preclinical experiments and initial clinical trials to critically assess both the potential and current limitations of adoptive transfer of donor T-cells sensitized to selected minor alloantigens of the host or to peptide epitopes of proteins, differentially expressed by clonogenic leukemia cells, such as the Wilms tumor protein, WT-1, as a strategy to treat or prevent recurrence of leukemia in the post-transplant period. ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3663256 Mon, 31 May 2010 23:00:00 +0100 3663256 http://www.medworm.com/index.php?rid=3663258&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20537906%26dopt%3DAbstract Authors: Wang L, Xiong Y, Bosselut R During the last step of alphabeta T cell development, thymocytes that have rearranged genes encoding TCR chains and express CD4 and CD8 coreceptors are selected on the basis of their TCR reactivity to escape programmed cell death and become mature CD4 or CD8 T cells. This process is triggered by intrathymic TCR signaling, that activates 'sensor' transcription factors 'constitutively' expressed in DP thymocytes. Eventually, TCR-signaled thymocytes evolve effector transcriptional circuits that control basal metabolism, migration, survival and initiation of lineage-specific gene expression. This review examines how components of the 'sensing' transcription apparatus responds to positive selection signals, and highlights important differences with matur... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3663258 Mon, 24 May 2010 23:00:00 +0100 3663258 http://www.medworm.com/index.php?rid=3663257&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20537907%26dopt%3DAbstract Authors: Dervović D, Zúñiga-Pflücker JC The thymus provides a unique set of cues for the effective selection and differentiation of CD4 and CD8 T-cells from a pool of immature thymocytes. Several approaches have been used to elucidate the complex set of intrathymic interactions that mediate these selection and differentiation events. Over the years, a number of different in vitro approaches have been developed and employed to assist in the identification of the cellular and molecular players that underpin thymic function. Here we provide an overview of the advances, which were obtained by in vitro approaches, to our understanding of the process of positive selection and CD4/CD8 lineage commitment. PMID: 20537907 [PubMed - as supplied by publisher] (Source: Seminars in I... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3663257 Mon, 24 May 2010 23:00:00 +0100 3663257 http://www.medworm.com/index.php?rid=3618336&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20510627%26dopt%3DAbstract Authors: Takahama Y, Nitta T, Mat Ripen A, Nitta S, Murata S, Tanaka K During T cell development in the thymus, a virgin repertoire of diverse TCRalphabeta recognition specificities in immature thymocytes is selected through positive and negative selection to form an immunocompetent and self-tolerant repertoire of mature T cells. Positive selection supports the survival of thymocytes that receive weak signals of low-avidity TCR engagement, whereas negative selection deletes potentially harmful self-reactive thymocytes upon high-avidity TCR engagement. Early studies have highlighted the role of TCR interaction with polymorphic MHC determinants in positive selection, while negative selection imposes TCR specificity to peptide antigens displayed by MHC molecules. However, recent advances ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3618336 Sun, 23 May 2010 23:00:00 +0100 3618336 http://www.medworm.com/index.php?rid=3590838&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20488726%26dopt%3DAbstract Authors: Dubensky TW, Reed SG The recent FDA approval of sipuleucel-T (Provenge((R))), a patient-specific immunotherapy for androgen-independent prostate cancer developed by Dendreon Corporation, has provided support for the concept of cellular immunotherapy as an approach to cancer treatment. Adjuvants are compounds that enhance the potency of the antigen-specific immune response and can be an essential component of an efficacious vaccine. Cervarix is a prophylactic vaccine against human papilloma virus (HPV) types 16 and 18, which can cause cervical cancer, and recently received approval from the FDA, due in part to the protective immunity it conferred against not only HPV types contained in the vaccine but in addition to oncogenic HPV strains that were not contained in the vaccine. ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3590838 Mon, 17 May 2010 23:00:00 +0100 3590838 http://www.medworm.com/index.php?rid=3590837&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20488727%26dopt%3DAbstract Authors: Nakayama T, Yamashita M In the periphery, upon antigen recognition by alphabetaTCR, naïve CD4 T cells undergo functional differentiation and acquire the ability to produce a specific set of cytokines. At least four Th cell subsets, i.e., Th1, Th2, Th17 and iTreg cells have so far been identified and the differentiation of each subset is driven by distinct cytokine sets. Antigen recognition by TCR and the activation of the TCR-mediated signaling pathways that follows, however, are most critical for initiating Th cell differentiation. This review focuses on the TCR signal strength and the TCR-mediated signaling pathways that control the differentiation into these four Th cell subsets. PMID: 20488727 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3590837 Mon, 17 May 2010 23:00:00 +0100 3590837 http://www.medworm.com/index.php?rid=3585607&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20471282%26dopt%3DAbstract Authors: Lee SY, Stadanlick J, Kappes DJ, Wiest DL While insights into the molecular processes that specify adoption of the alphabeta and gammadelta fates are beginning to emerge, the basis for control of specification remains highly controversial. This review highlights the current models attempting to explain T lineage commitment. Recent observations support the hypothesis that the T cell receptor (TCR) provides instructive cues through differences in TCR signaling intensity and/or longevity. Accordingly, we review evidence addressing the importance of differences in signal strength/longevity, how signals differing in intensity/longevity may be generated, and finally how such signals modulate the activity of downstream effectors to promote the opposing developmental fates. PMID: ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3585607 Tue, 11 May 2010 23:00:00 +0100 3585607 http://www.medworm.com/index.php?rid=3585606&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20471283%26dopt%3DAbstract Authors: Wiest DL PMID: 20471283 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3585606 Tue, 11 May 2010 23:00:00 +0100 3585606 http://www.medworm.com/index.php?rid=3565735&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20466561%26dopt%3DAbstract Authors: Wong GW, Zúñiga-Pflücker JC A common bipotent thymocyte precursor gives rise to both lineages of T cells, alphabeta and gammadelta. However, the cell intrinsic and extrinsic factors that influence alphabeta- versus gammadelta-lineage bifurcation remain controversial. gammadelta T cells play a unique and vital role in host defense, from maintaining integrity at epithelial and mucosal barriers to their newly defined role as an important innate source of interleukin-17. Although a T cell receptor (TCR)-independent fate choice may take place, emerging data supports a model in which the differential signaling capacity of alphabeta and gammadeltaTCRs play an instructional role in specifying lineage fate, with strength of signal measured by the amount of ERK/MAPK pathway act... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3565735 Mon, 10 May 2010 23:00:00 +0100 3565735 http://www.medworm.com/index.php?rid=3557021&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20452783%26dopt%3DAbstract Authors: Hayes SM, Laird RM, Love PE Signaling by the gammadelta T cell receptor (TCR) is required not only for alphabeta/gammadelta lineage commitment but also to activate and elicit effector functions in mature gammadelta T cells. Notably, at both of these stages, the signal delivered by the gammadeltaTCR is more robust than the one delivered by either the preTCR or the alphabetaTCR. Recent studies now provide evidence that signaling by the gammadeltaTCR is also required at other stages during gammadelta T cell development. Remarkably, the strength of the gammadeltaTCR signal also plays a role at these other stages, as evidenced by the findings that genetic manipulation of gammadeltaTCR signal strength affects gammadelta T cell maturation and effector fate. In this review, we discuss... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3557021 Thu, 06 May 2010 23:00:00 +0100 3557021 http://www.medworm.com/index.php?rid=3557023&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20451408%26dopt%3DAbstract Authors: O'Brien RL, Born WK The gammadelta T lmphocytes are often divided into subsets based upon expression of certain TCR components. This division was initially made because gammadelta T cells residing in particular epithelia were found to show tissue specific differences in their TCRs. Many examples now show that gammadelta T cell subsets also appear to be biased to carry out particular functions. This suggests that particular gammadelta TCR types direct the cells to acquire a certain type of functional programming during thymic development. Here, we describe functionally distinct, TCR-defined gammadelta T cell subsets, and evidence that their functions are predetermined in the thymus. PMID: 20451408 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3557023 Tue, 04 May 2010 23:00:00 +0100 3557023 http://www.medworm.com/index.php?rid=3557022&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20451409%26dopt%3DAbstract Authors: Narayan K, Kang J The mechanism of T cell precursor commitment to the gammadelta or alphabeta T cell lineage remains unclear. While TCR signal strength has emerged as a key factor in lineage commitment based on TCR transgenic models, the entire TCR repertoire may not possess the same discriminatory power. A counterbalance to the TCR as the lineage determinant is the pre-existing heterogeneity in gene expression among precursors, which suggests that single precursors are unlikely to respond homogeneously to a given instructive signal. PMID: 20451409 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3557022 Tue, 04 May 2010 23:00:00 +0100 3557022 http://www.medworm.com/index.php?rid=3546106&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20447835%26dopt%3DAbstract Authors: Nedellec S, Bonneville M, Scotet E Human Vgamma9Vdelta2 T cells, a major innate-like peripheral T cell subset, are thought to play in vivo a key role in innate and adaptive immune responses to infection agents and tumors. Vgamma9Vdelta2 T cell activation is tightly regulated by a variety of activating or inhibitory receptors which are specific for constitutively expressed or stress-modulated ligands. However, the mechanisms and signal transduction pathways regulating their broad effector functions, such as cytotoxicity and cytokine responses, remain poorly understood. Here we provide an updated overview of the activation modalities of Vgamma9Vdelta2 T cells by highlighting the respective role played by T cell receptor (TCR) versus non-TCR stimuli, and focus on recent studies s... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3546106 Mon, 03 May 2010 23:00:00 +0100 3546106 http://www.medworm.com/index.php?rid=3546105&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20447836%26dopt%3DAbstract Authors: Kreslavsky T, von Boehmer H Two major T lymphocyte lineages - alphabeta and gammadelta T cells - develop in the thymus from common precursors. Differentiation of both lineages requires signals coming from TCRs. Development of alphabeta T cells is driven at early stages by signaling from the pre-TCR, most likely in a ligand-independent fashion, and later - by signals delivered by alphabetaTCRs binding to their ligands - classical or non-classical MHC molecules. gammadelta lineage cells likewise require TCR signaling for their differentiation. Recent work from several groups suggests that TCR signaling not only ensures the developmental progression towards alphabeta and gammadelta lineages but that signal strength instructs lineage fate: weaker TCR signal results in alphabeta an... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3546105 Mon, 03 May 2010 23:00:00 +0100 3546105 http://www.medworm.com/index.php?rid=3522985&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20430644%26dopt%3DAbstract Authors: Meyer C, Zeng X, Chien YH gammadelta T cells develop in the thymus before entering the periphery. Recent work suggests that thymic development does little to constrain gammadelta T cell antigen specificities, but instead determines their effector fate. When triggered through the T cell receptor, ligand-naïve gammadelta T cells produce IL-17, ligand-experienced cells make IFN-gamma and those that are strongly self-reactive make IL-4. Importantly, gammadelta T cells are able to make cytokines immediately upon TCR engagement. These characteristics allow gammadelta T cells to initiate an acute inflammatory response to pathogens and to host antigens revealed by injury. These advances warrant a fresh look at how gammadelta T cells may function in the immune system. PMID: 2043... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3522985 Mon, 26 Apr 2010 23:00:00 +0100 3522985 http://www.medworm.com/index.php?rid=3435361&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20356763%26dopt%3DAbstract Authors: Chiang CL, Benencia F, Coukos G Although cancer vaccines with defined antigens are commonly used, the use of whole tumor cell preparations in tumor immunotherapy is a very promising approach and can obviate some important limitations in vaccine development. Whole tumor cells are a good source of TAAs and can induce simultaneous CTLs and CD4(+) T helper cell activation. We review current approaches to prepare whole tumor cell vaccines, including traditional methods of freeze-thaw lysates, tumor cells treated with ultraviolet irradiation, and RNA electroporation, along with more recent methods to increase tumor cell immunogenicity with HOCl oxidation or infection with replication-incompetent herpes simplex virus. PMID: 20356763 [PubMed - as supplied by publisher] (Source: Se... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3435361 Sun, 28 Mar 2010 23:00:00 +0100 3435361 http://www.medworm.com/index.php?rid=3386807&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20299242%26dopt%3DAbstract Authors: Paterson Y, Guirnalda PD, Wood LM This review covers the use of the facultative intracellular bacteria, Listeriamonocytogenes and Salmonella enterica serovar typhimurium as delivery systems for tumor-associated antigens in tumor immunotherapy. Because of their ability to infect and survive in antigen presenting cells, these bacteria have been harnessed to deliver tumor antigens to the immune system both as bacterially expressed proteins and encoded on eukaryotic plasmids. They do this in the context of strong innate immunity, which provides the required stimulus to the immune response to break tolerance against those tumor-associated antigens that bear homology to self. Here we describe differences in the properties of these bacteria as vaccine vectors, a summary of the major ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3386807 Tue, 16 Mar 2010 00:00:00 +0100 3386807 http://www.medworm.com/index.php?rid=3374686&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20226686%26dopt%3DAbstract Authors: Schreiber TH, Raez L, Rosenblatt JD, Podack ER Despite enormous effort, promising pre-clinical data in animal studies and over 900 clinical trials in the United States, no cancer vaccine has ever been approved for clinical use. Over the past decade a great deal of progress has been in both laboratory and clinical studies defining the interactions between developing tumors and the immune system. The results of these studies provide a rationale that may help explain the failure of recent therapeutic cancer vaccines in terms of vaccine principles, in selecting which tumors are the most appropriate to target and instruct the design and implementation of state-of-the-art cancer vaccines. PMID: 20226686 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3374686 Wed, 10 Mar 2010 00:00:00 +0100 3374686 http://www.medworm.com/index.php?rid=3295160&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20172739%26dopt%3DAbstract Authors: Cerundolo V, Kronenberg M PMID: 20172739 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3295160 Fri, 19 Feb 2010 00:00:00 +0100 3295160 http://www.medworm.com/index.php?rid=3255512&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20138544%26dopt%3DAbstract Authors: Rast J, Litman G PMID: 20138544 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3255512 Thu, 04 Feb 2010 00:00:00 +0100 3255512 http://www.medworm.com/index.php?rid=3156701&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20056434%26dopt%3DAbstract Authors: Saha NR, Smith J, Amemiya CT All extant vertebrates possess an adaptive immune system wherein diverse immune receptors are created and deployed in specialized blood cell lineages. Recent advances in DNA sequencing and developmental resources for basal vertebrates have facilitated numerous comparative analyses that have shed new light on the molecular and cellular bases of immune defense and the mechanisms of immune receptor diversification in the "jawless" vertebrates. With data from these key species in hand, it is becoming possible to infer some general aspects of the early evolution of vertebrate adaptive immunity. All jawed vertebrates assemble their antigen-receptor genes through combinatorial recombination of different "diversity" segments into immunoglobulin or T-cell r... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3156701 Tue, 05 Jan 2010 00:00:00 +0100 3156701 http://www.medworm.com/index.php?rid=3137816&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20044272%26dopt%3DAbstract Authors: McKitrick TR, De Tomaso AW Allorecognition has been described in many metazoan phyla, from the sponges to the mammals. In vertebrates, allorecognition is a result of a MHC-based recognition event central to adaptive immunity. However, the origin of the adaptive immune system and the potential relationship to more primitive allorecognition systems is unclear. The colonial ascidian, Botryllus schlosseri, has been used as a model organism for the study of allorecognition for over a century, as it undergoes a natural transplantation reaction controlled by a single, highly polymorphic locus. Herein we will summarize our current understanding of the molecular mechanisms that underlie this innate allorecognition reaction. PMID: 20044272 [PubMed - as supplied by publisher] (Source... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3137816 Tue, 29 Dec 2009 00:00:00 +0100 3137816 http://www.medworm.com/index.php?rid=3125303&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20036144%26dopt%3DAbstract Authors: McFall-Ngai M, Nyholm SV, Castillo MG The squid-vibrio symbiosis is an experimental system being studied as a model of the chronic colonization of animal epithelia by bacterial partners. One principal question being asked with this model is: what is the role of the immune system in the dynamics of the onset and maintenance of the symbiotic state? This review focuses upon results of research to date, which have demonstrated that both cell-mediated and cell-free components of the innate immune system are involved in these processes. PMID: 20036144 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3125303 Wed, 23 Dec 2009 00:00:00 +0100 3125303 http://www.medworm.com/index.php?rid=3115666&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20022762%26dopt%3DAbstract Authors: Messier-Solek C, Buckley KM, Rast JP Detailed understanding of animal immunity derives almost entirely from investigations of vertebrates, with a smaller, but significant, contribution from studies in fruit flies. This limited phylogenetic scope has artificially polarized the larger view of animal immunity toward the complex adaptive immune systems of vertebrates on the one hand and systems driven by relatively small, stable families of innate receptors of insects on the other. In the past few years analyses of a series of invertebrate deuterostome genome sequences, including those from echinoderms and cephalochordates, sharply modify this view. These findings have far-reaching implications for characterizing the potential range of animal immunity and for inferring the evoluti... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3115666 Fri, 18 Dec 2009 00:00:00 +0100 3115666 http://www.medworm.com/index.php?rid=3067838&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19962909%26dopt%3DAbstract Authors: Vasan S, Tsuji M NKT cells are known to play a role against certain microbial infections, including malaria and HIV, two major global infectious diseases. NKT cells exhibit either protective or pathogenic role against malaria. They are depleted by HIV infection and have a direct pathogenic role against many opportunistic infections common in end-stage AIDS. This review discusses the various features of the interaction between NKT cells and malaria parasites and HIV, and the potential to harness this interaction for therapeutic and vaccine strategies. PMID: 19962909 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3067838 Thu, 03 Dec 2009 00:00:00 +0100 3067838 http://www.medworm.com/index.php?rid=3050759&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19948416%26dopt%3DAbstract Authors: Brigl M, Brenner MB Invariant natural killer T (iNKT) cells have evolved to recognize CD1d-presented lipid antigens and are known to play important roles during infection with bacterial, viral, protozoan, and fungal pathogens. The limited antigen specificity and reactivity to self- and foreign antigens distinguish iNKT cells from MHC-restricted T cells and bear similarity to innate-like lymphocytes, such as NK cells, gammadelta T cells, MZB and B1-B cells. This review summarizes how direct recognition of microbial lipids or synergistic stimulation by self-lipids and pro-inflammatory cytokines results in activation of these innate-like iNKT cell during infection. iNKT cell activation in the absence of foreign antigen recognition is unique for cells bearing TCRs and underscores ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3050759 Sat, 28 Nov 2009 00:00:00 +0100 3050759 http://www.medworm.com/index.php?rid=3044311&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19945889%26dopt%3DAbstract Authors: Godfrey DI, Pellicci DG, Patel O, Kjer-Nielsen L, McCluskey J, Rossjohn J alphabeta T cell receptors (TCRs) have traditionally been viewed as receptors for peptide antigens presented by either Major Histocompatibility Complex (MHC) class I (for CD8 T cells) or MHC class II (for CD4 T cells) antigen-presenting molecules. However, it is now clear that some T cell lineages express TCRs that are specialized for recognition of lipid-based antigens presented by the MHC class I-like CD1 family. Recently, the molecular basis for the TCR recognition of glycolipid antigens presented by CD1d has revealed an evolutionarily conserved-docking mode that is distinct from that of peptide-based recognition. T cells carrying these receptors follow a unique developmental pathway that results not ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3044311 Fri, 27 Nov 2009 00:00:00 +0100 3044311 http://www.medworm.com/index.php?rid=3044312&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19945296%26dopt%3DAbstract Authors: Venkataswamy MM, Porcelli SA In spite of their relatively limited antigen receptor repertoire, CD1d-restricted NKT cells recognize a surprisingly diverse range of lipid and glycolipid antigens. Recent studies of natural and synthetic CD1d-presented antigens provide an increasingly detailed picture of how the specific structural features of these lipids and glycolipids influence their ability to be presented to NKT cells and stimulate their diverse immunologic functions. Particularly for synthetic analogues of alpha-galactosylceramides which have been the focus of intense recent investigation, it is becoming clear that the design of glycolipid antigens with the ability to precisely control the specific immunologic activities of NKT cells is likely to be feasible. The emerging d... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3044312 Thu, 26 Nov 2009 00:00:00 +0100 3044312 http://www.medworm.com/index.php?rid=3034355&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19939703%26dopt%3DAbstract Authors: Fujii S, Motohashi S, Shimizu K, Nakayama T, Yoshiga Y, Taniguchi M Invariant natural killer T (iNKT) cells have adjuvant activity due to their ability to produce large amounts of IFN-gamma, which activates other cells in innate and acquired systems, and orchestrates protective immunity. Based on these adjuvant mechanisms, we developed iNKT cell-targeted adjuvant therapy and carried out a phase I/IIa trial on advanced lung cancer patients. The patient group with increased numbers of IFN-gamma-producing cells showed prolonged survival with a median survival time of 31.9 months. Sixty percent of the patients in this group survived for more than 2 years with only a primary treatment and without tumor progression and metastasis. PMID: 19939703 [PubMed - as supplied by publishe... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3034355 Mon, 23 Nov 2009 00:00:00 +0100 3034355 http://www.medworm.com/index.php?rid=3015947&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19926302%26dopt%3DAbstract Authors: Danska JS, Poussier P PMID: 19926302 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3015947 Tue, 17 Nov 2009 00:00:00 +0100 3015947 http://www.medworm.com/index.php?rid=3015946&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19926489%26dopt%3DAbstract Authors: Cheung YH, Loh C, Pau E, Kim J, Wither J Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by production of autoantibodies directed against nuclear antigens resulting in formation of immune complexes that deposit in multiple organs causing tissue damage. SLE is a complex genetic disease in which variations in multiple genes, each with a modest effect size, contribute to disease genesis. Given this genetic complexity, identification of the role of individual polymorphisms is challenging. In this context, studies of mouse models of lupus have been particularly informative. Here we review the findings arising from the study of gene deleted, transgenic and congenic lupus-prone mouse models. PMID: 19926489 [PubMed - as supplied by publisher] (... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3015946 Mon, 16 Nov 2009 00:00:00 +0100 3015946 http://www.medworm.com/index.php?rid=3015945&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19926490%26dopt%3DAbstract Authors: Rosenstiel P, Sina C, Franke A, Schreiber S Recent advances have enabled a comprehensive understanding of the genetic architecture of inflammatory bowel disease (IBD) with over 30 identified and replicated disease loci. The pathophysiological consequences of disease gene variants in Crohn disease and ulcerative colitis, the two main subentities of IBD, so far are only understood on the single disease gene level, yet complex network analyses linking the individual risk factors into a molecular risk map are still missing. In this review, we will focus on recent pathways and cellular functions that emerged from the genetic studies (e.g. innate immunity, autophagy) and delineate the existence of shared (e.g. IL23R, IL12B) and unique (e.g. NOD2 for CD) risk factors for the disease ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=3015945 Mon, 16 Nov 2009 00:00:00 +0100 3015945 http://www.medworm.com/index.php?rid=2832678&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19775910%26dopt%3DAbstract Authors: Zuvich RL, McCauley JL, Pericak-Vance MA, Haines JL Multiple sclerosis (MS) is an idiopathic autoimmune neurodegenerative disease. Like many common diseases, MS has a genetic component; however, as with most complex diseases, the genetic architecture may be influenced by heterogeneity, incomplete penetrance, polygenic inheritance, and environmental factors. This clinically complex disease has provided great challenges for geneticists over the years. Although the first consistent genetic association to MS (with HLA-DR*1501) was discovered more than 30 years ago, lack of consistently replicated genetic results has plagued the scientific community. New study design methods (particularly genome-wide associations studies [GWAS]) along with genome project data and larger datasets ha... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2832678 Sun, 20 Sep 2009 23:00:00 +0100 2832678 http://www.medworm.com/index.php?rid=2745943&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713124%26dopt%3DAbstract Authors: Bishop DG PMID: 19713124 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2745943 Mon, 24 Aug 2009 23:00:00 +0100 2745943 http://www.medworm.com/index.php?rid=2730767&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19699108%26dopt%3DAbstract Authors: Girardin SE, Philpott DJ PMID: 19699108 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2730767 Tue, 18 Aug 2009 23:00:00 +0100 2730767 http://www.medworm.com/index.php?rid=2671203&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19647448%26dopt%3DAbstract Authors: Loskog AS, Eliopoulos AG CD40 is a TNF receptor family member that is widely recognized for its prominent role in immune regulation and homeostasis. Expression of CD40 is not restricted to normal lymphoid cells but is also evident in the majority of haemopoietic and epithelial malignancies where it has been implicated in oncogenic events. Accumulating evidence, however, suggests that the CD40 pathway can be exploited for cancer therapy by virtue of its ability to stimulate the host anti-tumor immune response, normalize the tumor microenvironment and directly suppress the growth of CD40-positive tumors. Here, we provide an overview of the multifaceted functions of the CD40 pathway in cancer and its emerging role in the treatment of malignancy. PMID: 19647448 [PubMed - as su... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2671203 Wed, 29 Jul 2009 23:00:00 +0100 2671203 http://www.medworm.com/index.php?rid=2640604&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19628407%26dopt%3DAbstract Authors: Dugger K, Lowder TW, Tucker TA, Schwiebert LM Through the expression of inflammatory mediators and immune-related molecules, epithelial cells function as immune effector cells in a wide variety of tissues; the expression of the CD40 receptor on these cells contributes this role. Engagement of CD40 activates epithelial cells and results in their release of pro- and anti-inflammatory mediators as well as pro-fibrotic molecules. As such, epithelial CD40 has been implicated in the pathogenesis of inflammatory disorders, generation of self-tolerance, and rejection of allografts. PMID: 19628407 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2640604 Mon, 20 Jul 2009 23:00:00 +0100 2640604 http://www.medworm.com/index.php?rid=2622446&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616968%26dopt%3DAbstract Authors: Subauste CS The interaction between CD40 and CD154 regulates many aspects of cellular and humoral immunity. The CD40-CD154 pathway is important for resistance against a variety of parasites. Studies done with these pathogens have provided important insight into the various mechanisms by which this pathway enhances host protection, mechanisms by which pathogens subvert CD40 signaling, conditions in which the CD40-CD154 pathway promotes disease and on modulation of this pathway for immunotherapy. PMID: 19616968 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2622446 Thu, 16 Jul 2009 23:00:00 +0100 2622446 http://www.medworm.com/index.php?rid=2622447&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616449%26dopt%3DAbstract Authors: Engel D, Seijkens T, Poggi M, Sanati M, Thevissen L, Beckers L, Wijnands E, Lievens D, Lutgens E Atherosclerosis is a chronic disease of the large arteries that is responsible for the majority of cardiovascular events. In its pathogenesis, the immune system plays a pivotal role. The effectuation of the immune response through interactions between immune cells that is mediated by co-stimulatory molecules, determine atherosclerosis severity. This review will highlight the role of one of the most powerful co-stimulatory dyads, the CD154 (also known as CD40 ligand, CD40L)-CD40 dyad, in atherosclerosis. Its cell-type specific actions, signal transduction cascades and its therapeutic potentials will be discussed. PMID: 19616449 [PubMed - as supplied by publisher] (Source: Semina... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2622447 Wed, 15 Jul 2009 23:00:00 +0100 2622447 http://www.medworm.com/index.php?rid=2603280&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595612%26dopt%3DAbstract Authors: Peters AL, Stunz LL, Bishop GA CD40 is a tumor necrosis factor receptor superfamily member expressed by immune and non-immune cells. CD40:CD154 interactions mediate T-dependent B cell responses and efficient T cell priming. Thus, CD40 is a likely candidate to play roles in autoimmune diseases in which activated T and B cells cause pathology. Diseases in which CD40 plays a pathogenic role include autoimmune thyroiditis, type 1 diabetes, inflammatory bowel disease, psoriasis, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. This review discusses the role of CD40:CD154 interaction in human and mouse autoimmunity, human polymorphisms associated with disease incidence, and disrupting CD40:CD154 interactions as an autoimmune therapy. PMID: 19595612 [Pu... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2603280 Thu, 09 Jul 2009 23:00:00 +0100 2603280 http://www.medworm.com/index.php?rid=2573713&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19574059%26dopt%3DAbstract Authors: Hakonarson H, Grant SF Genome-wide association studies have delivered on the promise of uncovering genetic determinants of complex disease. In this review, we provide a summary of recent advances in the identification of multiple variants associated with autoimmune-mediated disorders; specifically type 1 diabetes and inflammatory bowel disease. Sixteen loci, all replicated in independent samples, have now been uncovered for type 1 diabetes and in excess of 40 for inflammatory bowel disease. The next steps are to identify the true causal variants underlying evidence of disease association and to leverage this information to improve diagnosis, prevention and cure of these diseases. PMID: 19574059 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2573713 Mon, 29 Jun 2009 23:00:00 +0100 2573713 http://www.medworm.com/index.php?rid=2528714&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19540774%26dopt%3DAbstract Authors: Suttles J, Stout RD Macrophages reside in all tissues as resident populations and as immigrants recruited in response to tissue injury, inflammation or pathogen invasion. Under normal conditions, macrophages contribute to tissue homeostasis and provide innate immune surveillance. Both macrophages and their progenitors, bone marrow-derived monocytes, constitutively express the tumor necrosis factor receptor superfamily member, CD40, and are capable of a robust response to CD40 ligation resulting in the induction or enhancement of expression of genes with a predominantly pro-inflammatory function. CD40 signaling in macrophages in the context of host responses to pathogens plays a crucial role in host defense. However, macrophage responses to CD40 ligation in the context of autoi... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528714 Wed, 17 Jun 2009 23:00:00 +0100 2528714 http://www.medworm.com/index.php?rid=2528717&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19539498%26dopt%3DAbstract Authors: Munroe ME CD40 stimulation on monocytes/macrophages, dendritic cells, and B-lymphocytes has been the subject of much study. It is well recognized that activation of CD40 on antigen presenting cells by its ligand, CD154, expressed on T-lymphocytes, contributes to the pro-inflammatory response necessary for eradication of infection, yet pathological in autoimmunity. However, there is evidence that CD40 is also expressed on T-lymphocytes and can act as a costimulatory molecule. While the exact role of CD40 on CD8 T cells remains controversial, it does appear to contribute to the adaptive immune response against infection. CD40 on CD4 T cells, on the other hand, plays a functional role in the autoimmune disease process. Further dissection of the exact nature and role of CD40 in T ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528717 Mon, 15 Jun 2009 23:00:00 +0100 2528717 http://www.medworm.com/index.php?rid=2528716&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19539499%26dopt%3DAbstract Authors: Brodsky IE, Monack D The host response against diverse bacterial pathogens involves activation of specialized immune cells and elaboration of pro-inflammatory cytokines that help to coordinate appropriate host defense. Members of the interleukin-1 (IL-1) cytokine family, IL-1beta and IL-18, are central players in this process. Extracellular release of the mature, active form of these cytokines requires their processing by the cysteine protease caspase-1, which therefore serves as a key regulator of the inflammatory response. In addition to its role in secretion of pro-inflammatory cytokines, caspase-1 is also required for a form of cell death, recently termed pyroptosis, that occurs in macrophages infected by certain bacterial pathogens. Caspase-1 itself is synthesized as a pr... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528716 Mon, 15 Jun 2009 23:00:00 +0100 2528716 http://www.medworm.com/index.php?rid=2528715&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19539500%26dopt%3DAbstract Authors: Nakhaei P, Genin P, Civas A, Hiscott J Viral and microbial pathogens contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface- and endosome-associated Toll-like receptors (TLRs). RNA virus infection is also detected through TLR-independent mechanisms. Early viral replicative intermediates are detected by two recently characterized cystolic viral RNA receptors-RIG-I and MDA-5. Both are DExDH/box RNA helicases, and RIG-I specifically recognizes 5'-triphosphate containing viral RNA and transmits signals that induce type I interferon-mediated host immunity against virus infection. In this review, we will focus on RIG-I-like receptor (RLR) signal transduction and the regulatory mechanisms - ubiquitination, deubiquitination, ISGyl... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528715 Mon, 15 Jun 2009 23:00:00 +0100 2528715 http://www.medworm.com/index.php?rid=2528718&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535268%26dopt%3DAbstract Authors: Arnoult D, Carneiro L, Tattoli I, Girardin SE Mitochondria have been long recognized for their key role in the modulation of cell death pathways. Thus, it is therefore not surprising that this organelle represents a recurrent target for pathogenic microbes, aiming to manipulate the fate of the infected host cell. More recently, mitochondria have been shown to serve as a crucial platform for innate immune signaling, as illustrated by the identification of MAVS (also known as IPS-1, VISA and Cardif), NLRX1 and STING as mitochondrial proteins. This review discusses the tight interplay between microbial infection, innate immune signaling and mitochondria. PMID: 19535268 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528718 Sun, 14 Jun 2009 23:00:00 +0100 2528718 http://www.medworm.com/index.php?rid=2528719&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19524453%26dopt%3DAbstract Authors: Ma DY, Clark EA In this review, we focus on the function of CD40-CD40L (CD154) interactions in the regulation of dendritic cell (DC)-T cell and DC-B cell crosstalk. In addition, we examine differences and similarities between the CD40 signaling pathway in DCs and other innate immune cell receptors, and how these pathways integrate DC functions. As research into DC vaccines and immunotherapies progresses, further understanding of CD40 and DC function will advance the applicability of DCs in immunotherapy for human diseases. PMID: 19524453 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528719 Wed, 10 Jun 2009 23:00:00 +0100 2528719 http://www.medworm.com/index.php?rid=2528721&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19502082%26dopt%3DAbstract Authors: Manicassamy S, Pulendran B The discovery of Toll-like receptors (TLRs), and their role in sensing infections represents one of the most seminal advances in immunology in recent years. It is now clear that TLRs play a fundamental role in innate recognition of microbes, and stimulate and tune the quality of the adaptive immune response. However, major knowledge gaps remain in our understanding of how TLRs regulate the development and persistence of T- and B-cell memory. Here, we review our current understanding of how TLR-signaling shapes the adaptive immune response, and highlight unanswered questions, the solution of which will be imperative in the rational exploitation of TLRs in vaccine design and immune therapy. PMID: 19502082 [PubMed - as supplied by publisher] (Source... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528721 Thu, 04 Jun 2009 23:00:00 +0100 2528721 http://www.medworm.com/index.php?rid=2528720&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19502083%26dopt%3DAbstract Authors: Hussey S, Travassos LH, Jones NL Autophagy is an evolutionary conserved cellular process during which cytoplasmic material is engulfed in double membrane vacuoles that then fuse with lysosomes, ultimately degrading their cargo. Emerging evidence, however, now suggests that autophagy can form part of our innate and adaptive immune defense programs. Recent studies have identified pattern recognition molecules as mediators of this process and shown that intracellular pathogens can interact with and even manipulate autophagy. Recent translational evidence has also implicated autophagy in the pathogenesis of several immune-mediated diseases, including Crohn disease. In this review, we present autophagy in the context of its role as an immune system component and effector and specul... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528720 Thu, 04 Jun 2009 23:00:00 +0100 2528720 http://www.medworm.com/index.php?rid=2528722&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19501527%26dopt%3DAbstract Authors: Cassel SL, Joly S, Sutterwala FS The innate immune system senses danger signals via evolutionary conserved receptors. The nucleotide-binding domain leucine-rich repeat containing receptor (NLR) family is a group of intracellular receptors that drive a wide variety of inflammatory responses. A number of the NLR family members can form inflammasomes, which are multiprotein complexes that can activate caspase-1 and ultimately lead to the processing and secretion of interleukin (IL)-1beta, IL-18 and IL-33. One of the best-studied members of the NLR family is NLRP3 for which a number of divergent activators have recently been described. These and other studies examining the NLRP3 inflammasome will be discussed in this review. PMID: 19501527 [PubMed - as supplied by publisher] (... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528722 Wed, 03 Jun 2009 23:00:00 +0100 2528722 http://www.medworm.com/index.php?rid=2528723&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19497760%26dopt%3DAbstract Authors: Vilaysane A, Muruve DA As a component of all living cells and microbes, it is not surprising that organisms have evolved mechanisms to detect foreign or aberrant DNA and trigger an innate immune response. TLR9 is an endosomal membrane bound receptor that is widely studied and the best understood DNA sensor. However, the existence of TLR9-independent DNA sensing pathways have been recognized for many years. Recently, novel cytosolic DNA sensors have been uncovered that include ZBP1 or DNA-dependent activator of interferon-regulatory factors (DAI) and a DNA sensing inflammasome consisting of the HIN200 protein, absent in melanoma 2 (AIM2). In combination with TLR9, these receptors provide a diverse repertoire of mechanisms to alert the cell to microbial DNA and possibly aberrant... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528723 Mon, 01 Jun 2009 23:00:00 +0100 2528723 http://www.medworm.com/index.php?rid=2528731&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19369094%26dopt%3DAbstract Authors: Strid J, Tigelaar RE, Hayday AC Although studies of the skin have provided fundamental models for innate and adaptive immune surveillance of body surfaces, there remains relatively little understanding of the role that epithelial cells play in sensing infection and/or organ dysfunction, and the pathways available to them to communicate with local and systemic immune cells. In particular, evidence is emerging for a novel stress response initiated by local lymphocytes, rather than dendritic cells, and based on their recognition of epithelial stress-induced antigens. Its consequences are to sustain tissue integrity by providing immunoprotection and novel modes of immunoregulation, whereas its dysregulation may promote body surface immunopathologies. PMID: 19369094 [PubMed - i... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528731 Sun, 31 May 2009 23:00:00 +0100 2528731 http://www.medworm.com/index.php?rid=2528730&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19386512%26dopt%3DAbstract Authors: Marks BR, Craft J CD4+ T(H)17 cells display a featured role in barrier immunity. This effector population of T cells is important for clearance of microorganisms but can also promote autoimmunity at barrier sites. Recent work has indicated that these effector cells share a pathway with CD4+ regulatory T cells (T(R) cells) that also have a critical function in barrier protection and immune regulation. The development and function of T(H)17 cells, and their relationship with T(R) cells are discussed. PMID: 19386512 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528730 Sun, 31 May 2009 23:00:00 +0100 2528730 http://www.medworm.com/index.php?rid=2528729&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19386513%26dopt%3DAbstract Authors: van Wijk F, Cheroutre H The epithelium of the gastrointestinal tract, which represents the greatest body surface area exposed to the outside environment, is confronted with a plethora of foreign and potentially harmful antigens. Consequently, the immune system of the gut faces the daunting task of distinguishing harmless dietary proteins and commensal bacteria from potentially dangerous pathogens, and of then responding accordingly. Mucosal T cells play a central role in maintaining barrier function and controlling the delicate balance between immune activation and immune tolerance. This review will focus on the unique features of mucosal T cell subsets that reside in the epithelium and lamina propria of the gut. PMID: 19386513 [PubMed - in process] (Source: Seminars in Im... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528729 Sun, 31 May 2009 23:00:00 +0100 2528729 http://www.medworm.com/index.php?rid=2528727&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19446471%26dopt%3DAbstract Authors: Hayday AC, Spencer J PMID: 19446471 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528727 Sun, 31 May 2009 23:00:00 +0100 2528727 http://www.medworm.com/index.php?rid=2528724&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19493685%26dopt%3DAbstract Authors: Tapping RI The expansion of sensing function by cell surface Toll-like receptors (TLRs) has grown to include not only more diverse viral, bacterial, fungal and protozoan surface components, but also a plethora of endogenous molecules arising from host cell and tissue damage as well as the inflammatory response itself. This flexibility in recognition is accommodated not only by physical and structural features of the TLRs themselves, but also by additional innate immune receptors, soluble molecules and subcellular trafficking mechanisms. These events have begun to reveal a remarkable plasticity and complexity within this critical arm of the host innate immune system. PMID: 19493685 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528724 Sun, 31 May 2009 23:00:00 +0100 2528724 http://www.medworm.com/index.php?rid=2528725&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19447046%26dopt%3DAbstract Authors: Wang J, Wicker LS, Santamaria P Type 1 diabetes (T1D) is an organ-specific autoimmune disease featured by destruction of the insulin producing beta-cells of the pancreas by autoreactive T-lymphocytes. Putative environmental triggers conspire with a constellation of genetic elements scattered throughout the genome to elicit a multifactorial autoimmune response involving virtually every cell type of the immune system against pancreatic beta-cells. Recent highly powered genome-wide association studies have confirmed and identified fifteen chromosomal regions harboring several candidate T1D-associated gene loci. Here, we summarize what we know about the genetics of T1D with an emphasis on the contributions of mouse Il2 and human IL2RA polymorphisms and the IL-2-IL-2R pathway to au... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528725 Wed, 13 May 2009 23:00:00 +0100 2528725 http://www.medworm.com/index.php?rid=2528728&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19443237%26dopt%3DAbstract Authors: Heap GA, van Heel DA Coeliac disease is a common complex disease caused by a dietary intolerance to wheat gluten. Susceptibility is determined by both environmental and genetic factors. Coeliac disease results from complex interactions between the innate immune system, an adaptive T and B cell response and the mucosal barrier where inflammation is ultimately manifested. Genetic variants within the HLA region are well established, while variants outside of the HLA region have recently been identified. These variants are beginning to enhance our understanding of the immunology of the condition. This review focuses on the immunological pathogenesis of coeliac disease with special reference to the influence of genetic susceptibility on disease development. PMID: 19443237 [PubM... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528728 Tue, 12 May 2009 23:00:00 +0100 2528728 http://www.medworm.com/index.php?rid=2528726&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19446472%26dopt%3DAbstract Authors: Li Y, Begovich AB Talk of numerous genetic risk factors for rheumatoid arthritis (RA) and psoriasis has been percolating for years, but with the exception of the human leukocyte antigen (HLA) region, none have been definitively identified. Recently the results of multiple, well powered, genetic case-control studies have begun to appear providing convincing statistical evidence for at least ten non-HLA related risk genes or loci (C5/TRAF1, CD40, CTLA4, KIF5A/PIP4K2C, MMEL1/TNFRSF14, PADI4, PRKCQ, PTPN22, STAT4, and TNFAIP3/OLIG3) for RA and six (IL12B, IL13, IL23R, STAT2/IL23A, TNFAIP3, and TNIP1) for psoriasis. These initial, novel findings are beginning to shed light on the molecular pathways pertinent to the individual diseases and highlight the pleiotropic effects of severa... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2528726 Tue, 12 May 2009 23:00:00 +0100 2528726 http://www.medworm.com/index.php?rid=2285945&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19298945%26dopt%3DAbstract Authors: Schoenberger SP PMID: 19298945 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2285945 Tue, 24 Mar 2009 17:53:10 +0100 2285945 http://www.medworm.com/index.php?rid=2285944&cid=s_37055_3_f&fid=37055&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19298946%26dopt%3DAbstract Authors: Farber DL Memory T cells exhibit low activation thresholds and rapid effector responses following antigen stimulation, contrasting naive T cells with high activation thresholds and no effector responses. Signaling mechanisms for the distinct properties of naive and memory T cells remain poorly understood. Here, I will discuss new results on signal transduction in naive and memory T cells that suggest proximal control of activation threshold and a distinct biochemical pathway to rapid recall. The signaling and transcriptional pathways controlling immediate effector function in memory T cells closely resemble pathways for rapid effector cytokine production in innate immune cells, suggesting memory T cells use innate pathways for efficacious responses. PMID: 19298946 [PubMed ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2285944 Tue, 24 Mar 2009 17:52:27 +0100 2285944