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. Sun, 21 Mar 2010 13:39:37 +0100 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 http://www.medworm.com/index.php?rid=2250693&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%3D19269850%26dopt%3DAbstract Authors: Macleod MK, Clambey ET, Kappler JW, Marrack P Immunological memory provides the basis for successful vaccines. It is important to understand the properties of memory cells. There is much known about the phenotype and functions of memory CD8 T cells, less about memory B cells, while CD4 memory T cells have proved difficult to study. Differences in the types of memory CD4 cells studied and the difficulties of tracking the small number of cells have led to conflicting and unclear results. Here we discuss the different systems used to study CD4 memory cells and ask whether, and in what circumstances, memory CD4 cells could provide protection against infections. PMID: 19269850 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2250693 Fri, 06 Mar 2009 05:00:00 +0100 2250693 http://www.medworm.com/index.php?rid=2250692&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%3D19269851%26dopt%3DAbstract Authors: Nakayama T, Yamashita M The maintenance of memory CD4 T cells is crucial for the establishment of immunological memory. The Polycomb (PcG) and Trithorax group (TrxG) genes control key developmental regulators such as the homeobox genes, and these two antagonize each other in the same developmental processes. Recently, PcG gene Bmi1 has been found to control memory Th1/Th2 cell survival and TrxG gene MLL is to control the maintenance of memory Th2 cell function selectively. Therefore, in memory CD4 T cells, PcG and TrxG genes appear to control distinct processes in a distinct manner, which indicates a novel regulatory feature of the PcG/TrxG genes. PMID: 19269851 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2250692 Fri, 06 Mar 2009 05:00:00 +0100 2250692 http://www.medworm.com/index.php?rid=2250691&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%3D19269852%26dopt%3DAbstract Stem cell-like plasticity of naïve and distinct memory CD8(+) T cell subsets. Semin Immunol. 2009 Mar 6; Authors: Stemberger C, Neuenhahn M, Gebhardt FE, Schiemann M, Buchholz VR, Busch DH Most models regarding the 'clonal' origin of CD8(+) T cell effector and memory subset diversification suggest that during the first contact of a naïve T cell with the priming antigen-presenting cell major decisions for subsequent differentiation are made. Data using novel single-cell T cell tracking technologies demonstrate that a single naïve CD8(+) T cell can give rise to virtually all different subtypes of effector and memory T cells, and direct major determinants of subset diversification to the time period beyond the first cell division. Thereby, some 'stem cell-like' char... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2250691 Fri, 06 Mar 2009 05:00:00 +0100 2250691 http://www.medworm.com/index.php?rid=2250694&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%3D19269192%26dopt%3DAbstract Authors: D'Cruz LM, Rubinstein MP, Goldrath AW One outcome of infection is the formation of long-lived immunological memory, which provides durable protection from symptomatic re-infection. In response to infection or vaccination, T cells undergo dramatic proliferation and differentiate into effector T cells that mediate removal of the pathogen. Following pathogen clearance, the majority of effector cells die, restoring lymphocyte homeostasis. However, a small number of antigen-specific cells survive and seed the memory T cell population. Here, we focus on recent advances in identifying the key proteins and transcription factors that allow a portion of effector CD8(+) T cells to persist after contraction of the immune response, forming a memory cell population programmed for long-term ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2250694 Thu, 05 Mar 2009 05:00:00 +0100 2250694 http://www.medworm.com/index.php?rid=2250695&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%3D19268606%26dopt%3DAbstract Authors: Boesteanu AC, Katsikis PD The activation and expansion of naïve T cells require costimulatory signals provided by CD28 and TNF family members. In contrast, for many years it was believed that memory T cells do not require CD28 costimulation for expansion during secondary responses. This was based on in vitro experiments that suggested the re-activation of memory T cells is somewhat independent of costimulation. Recent in vivo evidence, however, has challenged this and shown that both CD4+ and CD8+ memory T cells require CD28 costimulation for maximal expansion and pathogen clearance. This requirement has important implications for host immunity, vaccine development and immunotherapeutics. PMID: 19268606 [PubMed - as supplied by publisher] (Source: Seminars in Immunolo... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2250695 Wed, 04 Mar 2009 05:00:00 +0100 2250695 http://www.medworm.com/index.php?rid=2233800&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%3D19250840%26dopt%3DAbstract Authors: Conrad C, Meller S, Gilliet M Plasmacytoid dendritic cells (pDCs) are specialized sensors of viral nucleic acids that initiate protective immunity through the production of type I interferons (IFNs). Normally, pDCs fail to sense host-derived self-nucleic acids but do so when self-nucleic acids form complexes with endogenous antimicrobial peptides produced in damaged skin. Whereas regulated expression of antimicrobial peptides may lead to pDC activation and protective immune responses to skin injury, overexpression of antimicrobial peptides in psoriasis drives excessive sensing of self-nucleic acids by pDCs resulting in IFN-driven autoimmunity. In skin tumors, pDCs are unable to sense self-nucleic acids; however, therapeutic activation of pDCs by synthetic nucleic acids or anal... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2233800 Thu, 26 Feb 2009 05:00:00 +0100 2233800 http://www.medworm.com/index.php?rid=2216987&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%3D19237300%26dopt%3DAbstract Authors: Kaser A, Blumberg RS The unfolded protein response as a consequence of endoplasmic reticulum (ER) stress has recently been implicated as a novel mechanism that may lead to inflammatory bowel disease (IBD). Impairment of proper ER stress resolution in highly secretory Paneth and, to a lesser extent, goblet cells within the epithelium can primarily lead to intestinal inflammation. An inability to manage ER stress may not only be a primary originator of intestinal inflammation as exemplified by genetic polymorphisms in XBP1 that are associated with IBD but also a perpetuator of inflammation when ER stress is induced secondarily to inflammatory mediators or microbial factors. Furthermore, ER stress pathways may interact with other processes that lead to IBD, notably autophagy. ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2216987 Sat, 21 Feb 2009 05:00:00 +0100 2216987 http://www.medworm.com/index.php?rid=2211323&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%3D19233686%26dopt%3DAbstract Authors: Spencer J, Barone F, Dunn-Walters D The organised gut associated lymphoid tissue (GALT) exists adjacent to an extensive and diverse luminal flora. The follicle associated epithelium and associated dendritic cells and lymphocytes form a tightly fortified gateway between the flora and the host that permits connectivity between them and chronic activation of the lymphoid compartment. As a consequence, plasma cell precursors are generated continuously, and in abundance, in GALT by clonal proliferation. Clonal proliferation alone on this scale would reduce the spectrum of B cell specificity. To compensate, GALT also houses molecular machinery that diversifies the receptor repertoire by somatic hypermutation, class switch recombination and receptor revision. These three processes of... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2211323 Fri, 20 Feb 2009 05:00:00 +0100 2211323 http://www.medworm.com/index.php?rid=2211324&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%3D19231234%26dopt%3DAbstract Authors: Meresse B, Cerf-Bensussan N One arm of the gut-associated immune system is represented by a vast collection of T lymphocytes which participate in the subtle interplay between innate and adaptive immune mechanisms and maintain homeostasis at the main body external surface. Mounting data are providing exciting new insight into the innate-like mechanisms which enable intestinal T cells to rapidly sense local conditions and which broaden the spectrum of their functions and regulation at this strategic location. Herein we discuss how innate-like T cell recognition by unconventional T cell subsets and expression of innate NK receptors might modulate immune T cell responses in the human normal or diseased intestine. PMID: 19231234 [PubMed - as supplied by publisher] (Source: Semi... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2211324 Thu, 19 Feb 2009 05:00:00 +0100 2211324 http://www.medworm.com/index.php?rid=2200891&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%3D19223202%26dopt%3DAbstract Authors: Wissinger E, Goulding J, Hussell T Innate immunity at mucosal surfaces requires additional restraint to prevent inflammation to innocuous antigens or commensal microorganisms. The threshold above which airway macrophages become activated is raised by site-specific factors including the receptors for transforming growth factor beta, interleukin 10 and CD200; the ligands for which are produced by, or expressed on, respiratory epithelium. We discuss such site-specific regulation and how this is continually altered by prior infections. Resetting of innate reactivity represents a strategy for limiting excessive inflammation, but in some may pre-dispose to secondary bacterial pneumonia. PMID: 19223202 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=2200891 Fri, 13 Feb 2009 05:00:00 +0100 2200891 http://www.medworm.com/index.php?rid=1996742&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%3D19036608%26dopt%3DAbstract Authors: Parham P In primates and cattle two ancient killer-cell immunoglobulin-like receptor (KIR) lineages independently evolved to become diverse NK cell receptors. In mice, KIR genes were sidelined to the X chromosome, a possible consequence of pathogen-mediated selection on the receptor for IgA-Fc. In humans, KIR uniquely form two omnipresent haplotype groups (A and B), postulated here to play complementary and necessary roles in immune defense and reproduction. The basis of KIR3DL1/S1 polymorphism is three ancient lineages maintained by long-term balancing selection and present in all human populations. Conserved and variable NK cell receptors produce structurally diverse NK cell receptor repertoires within a defined range of missing-self-response. PMID: 19036608 [PubMed - as... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1996742 Mon, 24 Nov 2008 05:00:00 +0100 1996742 http://www.medworm.com/index.php?rid=1934339&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%3D18977671%26dopt%3DAbstract Authors: Dissen E, Fossum S, Hoelsbrekken SE, Saether PC Natural killer (NK) cells discriminate between normal syngeneic cells and infected, neoplastic or MHC-disparate allogeneic cells. The reactivity of NK cells appears to be regulated by a balance between activating receptors that recognize non-self or altered self, and inhibitory receptors recognizing normal, self-encoded MHC class I molecules. Subfamilies of NK receptors undergo rapid evolution, and appear to co-evolve with the MHC. We here review present views on the evolution and function of NK cell receptors, with an emphasis on knowledge gained in cattle and rodents. PMID: 18977671 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1934339 Fri, 31 Oct 2008 04:00:00 +0100 1934339 http://www.medworm.com/index.php?rid=1934338&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%3D18977672%26dopt%3DAbstract Authors: Schreiber H PMID: 18977672 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1934338 Fri, 31 Oct 2008 04:00:00 +0100 1934338 http://www.medworm.com/index.php?rid=1915024&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%3D18951039%26dopt%3DAbstract Authors: Neller MA, López JA, Schmidt CW Progress in tumor immunology has not been translated to effective immunotherapies for cancer. Most of the current effort in basic and clinical research concentrates on generating effective immune responses against model or well characterized antigens, yet vaccines targeting defined antigens have been less clinically successful than those based on whole tumor cells or their extracts. This review considers characteristics of proteins that determine how effectively they might serve as targets of immune control, and how different sources of antigens have fared in clinical trials. PMID: 18951039 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1915024 Wed, 22 Oct 2008 04:00:00 +0100 1915024 http://www.medworm.com/index.php?rid=1907863&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%3D18948016%26dopt%3DAbstract Authors: Pyzik M, Kielczewska A, Vidal SM The complex interaction between natural killer (NK) cells and cytomegalovirus is a paradigm of the co-evolution between genomes of large DNA viruses and their host immune systems. Both human and mouse cytomegalovirus posses numerous mechanisms to avoid NK cell detection. Linkage studies, positional cloning and functional studies in mice and cells, have led to the identification of key genes governing resistance to cytomegalovirus, including various NK cell activating receptors of major histocompatibility complex (MHC) class I. These receptors, however, seem to require either viral or host MHC class I molecules to operate recognition and elimination of the cytomegalovirus-infected cell leading to host resistance. Here we will review the genes an... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1907863 Tue, 21 Oct 2008 04:00:00 +0100 1907863 http://www.medworm.com/index.php?rid=1907862&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%3D18948017%26dopt%3DAbstract Authors: Rogers SL, Viertlboeck BC, Göbel TW, Kaufman J Natural killer (NK) activity has been examined in birds for over 30 years, but evidence that avian NK activity plays crucial roles in disease is only suggestive. In chickens, NK activity is mediated by TCR0 cells in the intestinal epithelium, but elsewhere subsets of alphabeta and gammadelta T cells (NKT cells) may be more important. There are few lectin-like NK receptor genes, located in the genomic region syntenic with the natural killer complex (NKC) as well as the major histocompatibility complex (MHC). In contrast, a huge number of Ig-like receptor genes are located in a region syntenic with the leukocyte receptor complex (LRC). PMID: 18948017 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1907862 Tue, 21 Oct 2008 04:00:00 +0100 1907862 http://www.medworm.com/index.php?rid=1895558&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%3D18938087%26dopt%3DAbstract Authors: Makrigiannis AP, Parham P PMID: 18938087 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1895558 Sat, 18 Oct 2008 04:00:00 +0100 1895558 http://www.medworm.com/index.php?rid=1880140&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%3D18849172%26dopt%3DAbstract Authors: Iwata M Vitamin A deficiency causes a marked reduction in the number of T and B cells in the small intestinal tissues. The vitamin A metabolite retinoic acid imprints lymphocytes with gut-homing specificity upon antigenic stimulation. In the small intestinal lamina propria, Peyer's patches, and mesenteric lymph nodes, there are dendritic cells capable of producing retinoic acid. Their capacity depends on the expression of retinal dehydrogenases (RALDH). RALDH2, encoded by Aldh1a2, is a major isoform of RALDH in the intestinal dendritic cells under specific pathogen-free conditions, and can be induced by multiple factors constitutively present or induced in the small intestinal microenvironment. PMID: 18849172 [PubMed - as supplied by publisher] (Source: Seminars in Immunol... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1880140 Fri, 10 Oct 2008 04:00:00 +0100 1880140 http://www.medworm.com/index.php?rid=1859758&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%3D18838279%26dopt%3DAbstract Authors: Iwata M PMID: 18838279 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1859758 Sat, 04 Oct 2008 04:00:00 +0100 1859758 http://www.medworm.com/index.php?rid=1837478&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%3D18819820%26dopt%3DAbstract Authors: Ross AC, Chen Q, Ma Y Antibody production is crucial for a successful vaccine response. Beyond the ability of vitamin A (VA) and its active metabolite, all-trans-retinoic acid (RA) to restore growth in VA-deficient animals, supplementation with VA and/or treatment with RA can augment antibody responses in both VA-deficient and VA-adequate animals. RA alone, and in combination with stimuli that are ligands for the Toll-like receptor family, can augment the adaptive immune response leading to a heightened primary antibody response, and a stronger recall response upon restimulation. Mechanisms may include regulation of cell populations, type 1/type 2 cytokines, and B cell-related transcription factors, leading to accelerated B cell maturation. PMID: 18819820 [PubMed - as supp... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1837478 Wed, 24 Sep 2008 04:00:00 +0100 1837478 http://www.medworm.com/index.php?rid=1826174&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%3D18809338%26dopt%3DAbstract Authors: Mucida D, Park Y, Cheroutre H The vitamin A metabolites, including retinoic acid (RA), form ligands for retinoic acid-related nuclear receptors and together they play pleiotropic roles in various biological processes. Recently, we described that RA also functions as a key modulator of transforming growth factor-beta (TGF-beta)-driven immune deviation, capable of suppressing the differentiation of interleukin-17 secreting T helper cells (T(H)17) and conversely promoting the generation of Foxp3(+) T regulatory (Treg) cells. This review will focus on the role of RA in the reciprocal TGF-beta-driven differentiation of T(H)17 and Treg and on the importance of such regulatory mechanism to control a functional immune system, in particular at the mucosal interface of the intestine. ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1826174 Sat, 20 Sep 2008 04:00:00 +0100 1826174 http://www.medworm.com/index.php?rid=1815711&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%3D18804386%26dopt%3DAbstract Authors: Mora JR, von Andrian UH Antibody-secreting cells (ASCs) lodging in the mucosa of the small intestine are derived from activated B cells that are thought to arise in gut-associated lymphoid tissues (GALT). Upon leaving the GALT, B cells return to the blood where they must express the gut-homing receptors alpha4beta7 and CCR9 in order to emigrate into the small bowel. Recent evidence indicates that gut-associated dendritic cells (DCs) in GALT induce gut-homing receptors on B cells via a mechanism that depends on the vitamin A metabolite retinoic acid (RA). In addition, although ASC associated with other mucosal tissues secrete IgA in an RA-independent fashion, the presence of high levels of RA in intestine and GALT can promote B cell class switching to IgA and thus, boost the pr... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1815711 Wed, 17 Sep 2008 04:00:00 +0100 1815711 http://www.medworm.com/index.php?rid=1782849&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%3D18778953%26dopt%3DAbstract Authors: Manicassamy S, Pulendran B Dendritic cells (DCs) control the strength and quality of antigen-specific T and B cell responses. Recent advances point to a novel mechanism, in which metabolism of vitamin A into retinoic acid (RA) in DCs, regulate critical parameters of lymphocyte differentiation. First, RA enhances the induction of Foxp3(+) T regulatory cells by DCs. Thus, specific subsets of intestinal DCs and macrophages constitutively express RA synthesizing enzymes, and induce T regulatory cells. In addition, RA programs DCs to imprint mucosal homing properties on activated T and B cells, and enhanced induction of immunoglobulin-A (IgA) by B cells. Here, we review these recent advances, in the context of the pleiotropic effects of RA in regulating diverse biological processes... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1782849 Sat, 06 Sep 2008 04:00:00 +0100 1782849 http://www.medworm.com/index.php?rid=1770710&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%3D18771937%26dopt%3DAbstract Authors: Laslo P, Pongubala JM, Lancki DW, Singh H Considerable progress is being achieved in the analysis of gene regulatory networks that direct cell fate decisions within the hematopoietic system. In addition to transcription factors that are pivotal for cell fate specification and commitment, recent evidence suggests the involvement of microRNAs. In this review we attempt to integrate these two types of regulatory components into circuits that dictate cell fate choices leading to the generation of innate as well as adaptive immune cells. The developmental circuits are placed in the context of a revised scheme for hematopoiesis that suggests that both the innate (myeloid) and adaptive (lymphoid) lineages of the immune system arise from a common progenitor. PMID: 18771937 [PubMed... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1770710 Tue, 02 Sep 2008 04:00:00 +0100 1770710 http://www.medworm.com/index.php?rid=1769126&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%3D18768329%26dopt%3DAbstract Authors: Rothenberg EV, Scripture-Adams DD T-cell precursors remain developmentally plastic for multiple cell generations after entering the thymus, preserving access to developmental alternatives of macrophage, dendritic-cell, and even mast-cell fates. The underlying regulatory basis of this plasticity is that early T-cell differentiation depends on transcription factors which can also promote alternative developmental programs. Interfactor competition, together with environmental signals, keep these diversions under control. Here the pathways leading to several lineage alternatives for early pro-T-cells are reviewed, with close focus on the mechanisms of action of three vital factors, GATA-3, PU.1, and Notch-Delta signals, whose counterbalance appears to be essential for T-cell speci... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1769126 Tue, 02 Sep 2008 04:00:00 +0100 1769126 http://www.medworm.com/index.php?rid=1755198&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%3D18757210%26dopt%3DAbstract Authors: van Grevenynghe J, Halwani R, Chomont N, Ancuta P, Peretz Y, Tanel A, Procopio FA, Shi Y, Said EA, Haddad EK, Sekaly RP Lymph nodes (LNs) represent the principal site where antigen-specific memory T- and B-cell responses are primed and differentiated into memory and effector cells. During chronic viral infections such as HIV, these lymphoid tissues undergo substantial structural changes. These changes are mostly caused by an imbalanced cytokine milieu, hyper-immune activation and collagen deposition leading to fibrotic LNs. The structural integrity of the LNs is essential to prime and maintain memory responses. Because cellular signalling events both up- and down-stream of FOXO3a are critical to the generation and the maintenance of lymphocyte memory, this review will focus on... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1755198 Fri, 29 Aug 2008 04:00:00 +0100 1755198 http://www.medworm.com/index.php?rid=1755197&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%3D18760625%26dopt%3DAbstract Authors: Lane P, Sékaly RP PMID: 18760625 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1755197 Wed, 27 Aug 2008 04:00:00 +0100 1755197 http://www.medworm.com/index.php?rid=1746858&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%3D18752972%26dopt%3DAbstract Authors: Luc S, Buza-Vidas N, Jacobsen SE The prevailing model for adult hematopoiesis postulates that the first lineage commitment step results in a strict separation of common myeloid and common lymphoid pathways. However, the recent identification of granulocyte/monocyte (GM)-lymphoid restricted lymphoid-primed multipotent progenitors (LMPPs) and primitive common myeloid progenitors (CMPs) within the "HSC" compartment provide compelling support for establishment of independent GM-megakaryocyte/erythroid (GM-MkE) and GM-lymphoid commitment pathways as decisive early lineage fate decisions. These changes in lineage potentials are corroborated by corresponding changes in multilineage transcriptional priming, as LMPPs down-regulate MkE priming but become GM-lymphoid transcriptionally pr... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1746858 Mon, 25 Aug 2008 04:00:00 +0100 1746858 http://www.medworm.com/index.php?rid=1746859&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%3D18722139%26dopt%3DAbstract Authors: Lukin K, Fields S, Hartley J, Hagman J B lymphocytes are generated from hematopoietic stem cells in a series of steps controlled by transcription factors. One of the most important regulators of this process is early B cell factor (EBF). Multiple lines of evidence indicate that expression of EBF is a principle determinant of the B cell fate. In the absence of EBF, progenitor cells fail to express classical markers of B cells, including immunoglobulins. EBF drives B cell differentiation by activating the Pax5 gene and other genes required for the pre-B and B cell receptors. New evidence suggests that expression of EBF in common lymphoid progenitors directs B cell fate decisions. Specification and commitment of cells to the B cell lineage are further established by Pax5, which i... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1746859 Thu, 21 Aug 2008 04:00:00 +0100 1746859 http://www.medworm.com/index.php?rid=1726565&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%3D18715801%26dopt%3DAbstract Authors: Buckwalter MR, Srivastava PK The lessons are: (a) human cancers certainly respond to immunological manipulations. Efforts at human cancer immunotherapy are therefore worthwhile. (b) Prophylaxis is very different from therapy of pre-existing disease, and hence much enthusiasm should not be derived from successful prophylaxis studies. Even in case of infectious agents against which robust prophylaxis is routinely achieved, therapy is nearly impossible once the disease has established. (c) Studies with appropriate cancer models of mice and rats are useful. The notion that it is easy to cure cancers in mice is generally advanced the most confidently by those who have never cured a mouse of cancer by immunotherapy. (d) With a nod to James Carville, it is the antigen(s), stupid! We ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1726565 Tue, 19 Aug 2008 04:00:00 +0100 1726565 http://www.medworm.com/index.php?rid=1726564&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%3D18715802%26dopt%3DAbstract Authors: Gordy C, Dzhagalov I, He YW Retinoic acid plays a key role in the development and function of the immune system; however, the contribution of each of the three retinoic acid receptors (RARs) to the T cell immune response is not yet well understood. Of these receptors, both RARalpha and RARgamma are expressed in T lymphocytes. While possible functional redundancy thus complicates understanding of the role of each receptor in T cells, emerging data suggest that RARalpha and RARgamma function differently in thymocyte development and that RARgamma is required for both primary and secondary CD8(+) T cell immune responses. PMID: 18715802 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1726564 Tue, 19 Aug 2008 04:00:00 +0100 1726564 http://www.medworm.com/index.php?rid=1709672&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%3D18703353%26dopt%3DAbstract Authors: Ertesvåg A, Naderi S, Blomhoff HK Vitamin A protects against development of infectious diseases, and B cells are important players in this process. Keys to the protective role of retinoic acid (RA) against infections appear to be its ability to enhance antibody responses against T-cell dependent and independent type 2 antigens, as well as to locally stimulate IgA production in mucosal tissues. The elucidation of molecular mechanisms involved in RA-mediated regulation of proliferation and differentiation of B cells not only helps us to understand how RA differentially regulates subsets of B cells, but might also lead to more targeted treatment of selected immune disorders and B cell malignancies. PMID: 18703353 [PubMed - as supplied by publisher] (Source: Seminars in I... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1709672 Tue, 12 Aug 2008 04:00:00 +0100 1709672 http://www.medworm.com/index.php?rid=1692365&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%3D18684640%26dopt%3DAbstract Authors: Schietinger A, Philip M, Schreiber H From the earliest days in the field of tumor immunology three questions have been asked: do cancer cells express tumor-specific antigens, does the immune system recognize these antigens and if so, what is their biochemical nature? We now know that truly tumor-specific antigens exist, that they are caused by somatic mutations, and that these antigens can induce both humoral and cell-mediated immune responses. Because tumor-specific antigens are exclusively expressed by the cancer cell and are often crucial for tumorigenicity, they are ideal targets for anti-cancer immunotherapy. Nevertheless, the antigens that are targeted today by anti-tumor immunotherapy are not tumor-specific antigens, but antigens that are normal molecules also expressed... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1692365 Mon, 04 Aug 2008 04:00:00 +0100 1692365 http://www.medworm.com/index.php?rid=1664612&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%3D18656382%26dopt%3DAbstract Authors: Trowsdale J, Moffett A Both HLA class I molecules and their receptors on Natural Killer cells, the KIR molecules, are highly polymorphic. It is generally believed that this variation is driven in response to the role of these receptors and counter-receptors in resistance to disease. Uterine NK cells are the major maternal leukocyte population present within the decidua, and they express KIR2D receptors for HLA-C, the only polymorphic class I molecule on trophoblast. Genetic and functional data suggest that the maternal KIR/fetal HLA-C interaction in pregnancy may affect the delivery of an optimal blood supply to mother and fetus. The drive for novelty in HLA-C and KIR2D allelic diversity may relate not only to survival from infections but also to reproductive success. PMID... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1664612 Wed, 23 Jul 2008 04:00:00 +0100 1664612 http://www.medworm.com/index.php?rid=1646341&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%3D18640056%26dopt%3DAbstract Authors: Brown MG, Scalzo AA Natural killer (NK) cells play important roles in innate defense against infectious agents particularly viruses and also tumors. They mediate their effects through direct cytolysis, release of cytokines and regulation of subsequent adaptive immune responses. NK cells are equipped with sophisticated arrays of inhibitory and activation receptors that regulate their function. In this review we illustrate some of the major evolutionary relationships between NK cell receptors among different animal species and what some of the major mechanisms are that give rise to this diversity in receptor families, including the potential roles of pathogens such as viruses in driving receptor evolution. PMID: 18640056 [PubMed - as supplied by publisher] (Source: Seminars ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1646341 Thu, 17 Jul 2008 04:00:00 +0100 1646341 http://www.medworm.com/index.php?rid=1639422&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%3D18635379%26dopt%3DAbstract Authors: Kulkarni S, Martin MP, Carrington M Killer cell immunoglobulin-like receptors (KIR) are expressed on natural killer (NK) cells and subsets of T cells. The KIR genes are polymorphic and the KIR gene complex is polygenic with varying numbers of inhibitory and activating receptors. HLA class I molecules serve as ligands for the KIR. Interactions of the independently segregating KIR and HLA loci are important for recognition of targets by NK cells as well as NK cell 'licensing'. Several disease association studies indicate a role for interactions between these loci in infectious diseases, autoimmune/inflammatory disorders, cancer and reproduction. Emerging functional data supports a mechanism based on a continuum of inhibition to activation through various compound KIR-HLA genotyp... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1639422 Tue, 15 Jul 2008 04:00:00 +0100 1639422 http://www.medworm.com/index.php?rid=1631545&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%3D18620868%26dopt%3DAbstract Authors: Lederman MM, Margolis L Since the earliest days of the AIDS epidemic, clinicians and researchers have recognized the importance of lymphoid tissue both in the clinical manifestations of disease and in its pathogenesis. Generalized lymphadenopathy was one of the earliest harbingers of AIDS in the United States and over the past 27 years an increasing body of evidence has implicated the lymphoid organs as central to the pathogenesis of immune deficiency in chronic HIV-1 infection. In this essay, we will review some of the data that have been accumulated and propose a testable model that may reconcile them. PMID: 18620868 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1631545 Thu, 10 Jul 2008 04:00:00 +0100 1631545 http://www.medworm.com/index.php?rid=1577460&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%3D18595730%26dopt%3DAbstract Authors: Carlyle JR, Mesci A, Fine JH, Chen P, Bélanger S, Tai LH, Makrigiannis AP The Ly49 and Nkrp1 loci encode structurally and functionally related cell surface proteins that positively or negatively regulate natural killer (NK) cell-mediated cytotoxicity and cytokine production. Yet despite their clear relatedness and genetic linkage within the NK gene complex (NKC), these two multi-gene families have adopted dissimilar evolutionary strategies. The Ly49 genes are extremely polymorphic and evolutionarily dynamic, with distinct gene numbers, remarkable allelic diversity, and varying MHC-I-ligand specificities and affinities among different murine haplotypes. In contrast, the Nkrp1 genes have opted for overall conservation of genomic organization, sequences, and ligand specifici... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1577460 Tue, 01 Jul 2008 04:00:00 +0100 1577460 http://www.medworm.com/index.php?rid=1577459&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%3D18595731%26dopt%3DAbstract Authors: Estes JD, Haase AT, Schacker TW The hallmark of HIV/SIV infections is the progressive depletion of CD4+ T cells that ultimately renders the host incapable of defending against AIDS defining opportunistic infections and malignancies. Although many potential mechanisms have been proposed to explain CD4+ T cell loss, we review here the growing evidence that fibrotic 'scarring' and consequent damage to the lymphatic tissue niche contributes to CD4+ T cell decline and limits CD4+ T cell re-population with retroviral therapy. PMID: 18595731 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1577459 Tue, 01 Jul 2008 04:00:00 +0100 1577459 http://www.medworm.com/index.php?rid=1561283&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%3D18585056%26dopt%3DAbstract Authors: Greig KT, Carotta S, Nutt SL While it has long been known that the transcription factor c-Myb is an essential regulator of hematopoiesis, its precise molecular targets have remained elusive. Cell line studies suggest that c-Myb promotes proliferation and at the same time inhibits differentiation, however the early lethality of c-Myb deficient embryos precluded analysis of its role in adult hematopoiesis. Here we review insights derived from recently developed mouse models of c-Myb deficiency that are viable as adults. These studies reveal a complex array of functions for c-Myb in multiple hematopoietic cell types that will redefine our understanding of this crucial transcription factor. PMID: 18585056 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1561283 Wed, 25 Jun 2008 04:00:00 +0100 1561283 http://www.medworm.com/index.php?rid=1551809&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%3D18583148%26dopt%3DAbstract Authors: Lai AY, Kondo M Until the past few years, it has been thought that lymphoid and myeloid lineage segregation represents the first step of lineage restriction during hematopoiesis from hematopoietic stem cell. Recent investigation of the cell populations within multipotent progenitors in the bone marrow has led to new understanding of how hematopoietic stem cells diversify into different hematopoietic cell types. This review focuses on the recent advances in understanding the developmental events that occur during hematopoietic stem cell specification into the T and B lymphocyte lineages in adult mice. PMID: 18583148 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1551809 Tue, 24 Jun 2008 04:00:00 +0100 1551809 http://www.medworm.com/index.php?rid=1551810&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%3D18579409%26dopt%3DAbstract This article describes recent findings on the complexity of these molecular interactions and their consequences with respect to the regulation of cell fate decisions. We also describe recent findings from studies of genes expressed in the myeloid lineage (Pu.1 and csf1r) which highlight some of the molecular principles governing cell fate decisions at the epigenetic level. PMID: 18579409 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1551810 Mon, 23 Jun 2008 04:00:00 +0100 1551810 http://www.medworm.com/index.php?rid=1509024&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%3D18539480%26dopt%3DAbstract In this report, we summarize our results in humans targeting this mutation in two consecutive and one multi-institutional Phase II immunotherapy trials. These trials demonstrated that vaccines targeting EGFRvIII are capable of inducing potent T- and B-cell immunity in these patients, and lead to an unexpectedly long survival time. Most importantly, vaccines targeting EGFRvIII were universally successful at eliminating tumor cells expressing the targeted antigen without any evidence of symptomatic collateral toxicity. These studies establish the tumor-specific EGFRvIII mutation as a novel target for humoral- and cell-mediated immunotherapy in a variety of cancers. The recurrence of EGFRvIII-negative tumors in our patients, however, highlights the need for targeting a broader repertoire of t... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1509024 Fri, 06 Jun 2008 04:00:00 +0100 1509024 http://www.medworm.com/index.php?rid=1500153&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%3D18434190%26dopt%3DAbstract Authors: Förster R, Pabst O, Bernhardt G In the past decade accumulating evidence supported the view that the immune system should be regarded as trust consisting of several branches. In this review, we will first introduce the architectural features comprising the intestinal immune system emphasising its plasticity and subsequently discuss the concepts describing its development. We then focus on the chemokine/receptor system as a key integrator managing coordinated migration of and communication among the cells mediating intestinal immunity. Thus, chemokines control development and maintain functionality of the intestinal immune system that is required to perform the unique balancing act between tolerating food, curtailing commensals activities and eliminating pathogenic infecti... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500153 Mon, 21 Apr 2008 04:00:00 +0100 1500153 http://www.medworm.com/index.php?rid=1500154&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%3D18424165%26dopt%3DAbstract Authors: Hoorweg K, Cupedo T In contrast to our understanding of murine lymphoid organogenesis, detailed knowledge on the mechanisms of human lymph node development is virtually lacking. This is mainly due to the obvious difficulties that accompany research using human fetal organs. In this review we will highlight current knowledge on human lymph node and Peyer's patch development and will temporally align observations made in humans with data available from murine studies. In the final paragraphs we will put this knowledge in the context of human malignancies in which interactions between lymphocytes and stroma, resembling those seen in lymphoid organs, are recapitulated. PMID: 18424165 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500154 Thu, 17 Apr 2008 04:00:00 +0100 1500154 http://www.medworm.com/index.php?rid=1500155&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%3D18407516%26dopt%3DAbstract Authors: Lane P, Kim MY, Withers D, Gaspal F, Bekiaris V, Desanti G, Khan M, McConnell F, Anderson G Lymphoid tissue inducer cells (LTi) are known for their role in embryonic lymphoid tissue development. We have identified LTi in adult tissues including spleen and thymus, and provide evidence here for their presence in the submucosa of the intestine. From these observations it is clear that LTi play multiple roles in the adaptive immune system, notably the ability to recruit and sustain primed CD4 T cells in environments where they provide help to other cells. We speculate that their human equivalents could be potential targets for HIV infection and their destruction explains the pattern of loss of CD4 T cells. PMID: 18407516 [PubMed - as supplied by publisher] (Source: Seminars in... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500155 Fri, 11 Apr 2008 04:00:00 +0100 1500155 http://www.medworm.com/index.php?rid=1500156&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%3D18395462%26dopt%3DAbstract Authors: Lucas S, Coulie PG The choice of antigens to be used in cancer immunotherapy remains a crucial and difficult issue. This review highlights some properties of the different groups of human tumor antigens recognized by T lymphocytes, focusing on parameters that should influence this choice, such as tumor specificity and level of antigen expression. PMID: 18395462 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500156 Thu, 03 Apr 2008 04:00:00 +0100 1500156 http://www.medworm.com/index.php?rid=1500183&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%3D18035552%26dopt%3DAbstract Authors: Irvine DJ, Stachowiak AN, Hori Y The plasticity of the immune system is evident in the reorganization of secondary lymphoid organs during immune responses, lymphoid tissue neogenesis occurring during chronic inflammation or graft rejection, and the engineered lymphoid tissue formation induced by ectopic expression of single lymphoid tissue-associated genes. Approaches seeking to harness this plasticity for immunotherapy are under investigation, particularly by controlling immune cell recruitment and lymphoid tissue formation at tumor sites. By combining strategies from ectopic tissue induction models with methods from tissue engineering, new approaches for studying lymphoid tissue development and immunotherapy may be possible. PMID: 18035552 [PubMed - in process] (Source: ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500183 Tue, 01 Apr 2008 04:00:00 +0100 1500183 http://www.medworm.com/index.php?rid=1500178&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%3D18054498%26dopt%3DAbstract Authors: Babensee JE The interconnections between innate and adaptive immunity, with a focus on dendritic cells (DCs), in the context of combination products, are discussed. Biomaterials are shown to act as an adjuvant in the enhancement of the adaptive immune response to co-delivered antigen. Biomaterials are considered as agonists for DC maturation and several hypotheses as to the mechanism by which DCs recognize and respond to biomaterials are presented. There is the conceptualization of biomaterials with the idea of 'danger signals'. The goal is to design biomaterials to control DC phenotype and in this way control immune responses to combination products. PMID: 18054498 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500178 Tue, 01 Apr 2008 04:00:00 +0100 1500178 http://www.medworm.com/index.php?rid=1500175&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%3D18083531%26dopt%3DAbstract Authors: Badylak SF, Gilbert TW Biologic scaffold materials composed of mammalian extracellular matrix are commonly used in regenerative medicine and in surgical procedures for the reconstruction of numerous tissue and organs. These biologic materials are typically allogeneic or xenogeneic in origin and are derived from tissues such as small intestine, urinary bladder, dermis, and pericardium. The innate and acquired host immune response to these biologic materials and the effect of the immune response upon downstream remodeling events has been largely unexplored. Variables that affect the host response include manufacturing processes, the rate of scaffold degradation, and the presence of cross species antigens. This manuscript provides an overview of studies that have evaluated the im... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500175 Tue, 01 Apr 2008 04:00:00 +0100 1500175 http://www.medworm.com/index.php?rid=1500174&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%3D18160306%26dopt%3DAbstract Authors: Drukker M The derivation of human embryonic stem cell lines from blastocyst stage embryos, first achieved almost a decade ago, demonstrated the potential to prepare virtually unlimited numbers of therapeutically beneficial cells in vitro. Assuming that large-scale production of differentiated cells is attainable, it is imperative to develop strategies to prevent immune responses towards the grafted cells following transplantation. In this review, I will discuss recent advances in the production of pluripotent cell lines using three emerging techniques: somatic cell nuclear transfer into enucleated oocytes and zygotes, parthenogenetic activation of unfertilized oocytes and induction of pluripotency in somatic cells. Importantly, if these techniques can be harnessed for generati... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500174 Tue, 01 Apr 2008 04:00:00 +0100 1500174 http://www.medworm.com/index.php?rid=1500173&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%3D18162407%26dopt%3DAbstract Authors: Anderson JM, Rodriguez A, Chang DT The foreign body reaction composed of macrophages and foreign body giant cells is the end-stage response of the inflammatory and wound healing responses following implantation of a medical device, prosthesis, or biomaterial. A brief, focused overview of events leading to the foreign body reaction is presented. The major focus of this review is on factors that modulate the interaction of macrophages and foreign body giant cells on synthetic surfaces where the chemical, physical, and morphological characteristics of the synthetic surface are considered to play a role in modulating cellular events. These events in the foreign body reaction include protein adsorption, monocyte/macrophage adhesion, macrophage fusion to form foreign body giant cell... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500173 Tue, 01 Apr 2008 04:00:00 +0100 1500173 http://www.medworm.com/index.php?rid=1500171&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%3D18191409%26dopt%3DAbstract Authors: Jones KS Evidence is emerging that biomaterials cause inflammation by ligating innate immune receptors on antigen presenting cells. Although inflammation is usually viewed as detrimental, it has unexpected and potentially beneficial effects on fibrosis and transplant rejection. For example, the magnitude of inflammation due to a biomaterial is not predictive of the extent of fibrosis. Similarly, biomaterials do not always show adjuvancy. Some biomaterials suppressed T cell rejection responses in vivo and in vitro, while others non-specifically stimulated T cell proliferation. Understanding these complex inter-relationships is the key to designing a biomaterial that stimulates regeneration and induces tolerance in tissue engineering applications. PMID: 18191409 [PubMed - in... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500171 Tue, 01 Apr 2008 04:00:00 +0100 1500171 http://www.medworm.com/index.php?rid=1500170&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%3D18201895%26dopt%3DAbstract Authors: Swartz MA, Hubbell JA, Reddy ST The slow interstitial flow that drains fluid from the blood capillaries into the lymphatic capillaries provides transport of macromolecular nutrients to cells in the interstitium. We discuss herein how this flow also provides continuous access to immune cells residing in the lymph nodes of antigens from self or from pathogens residing in the interstitium. We also address mechanisms by which dendritic cells in the periphery sense interstitial flow to home efficiently into the lymphatics after activation, and how lymphatic endothelium can be activated by this flow, including how it can act as a lymphatic morphoregulator. Further, we present concepts on how interstitial flow can be exploited with biomaterial systems to deliver antigen and adjuvant ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500170 Tue, 01 Apr 2008 04:00:00 +0100 1500170 http://www.medworm.com/index.php?rid=1500168&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%3D18221888%26dopt%3DAbstract Authors: Sefton MV, Babensee JE, Woodhouse KA PMID: 18221888 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500168 Tue, 01 Apr 2008 04:00:00 +0100 1500168 http://www.medworm.com/index.php?rid=1500162&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%3D18243732%26dopt%3DAbstract Authors: Methe H, Hess S, Edelman ER The endothelium is a unique immunologic target. The first host-donor reaction in any cell, tissue or organ transplant occurs at the blood-tissue interface, the endothelium. When endothelial cells are themselves the primary component of the implant a second set of immunologic reactions arises. Injections of free endothelial cell implants elicit a profound major histocompatibility complex (MHC) II dominated immune response with significant sensitivity, cascade enhancement and immune memory. Endothelial cells embedded within three-dimensional matrices retain all the biosecretory capacity of quiescent endothelial cells. Perivascular implants of such cells are the most potent inhibitor of intimal hyperplasia and thrombosis following controlled vascular i... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500162 Tue, 01 Apr 2008 04:00:00 +0100 1500162 http://www.medworm.com/index.php?rid=1500167&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%3D18222702%26dopt%3DAbstract Authors: Fairfax KA, Kallies A, Nutt SL, Tarlinton DM Recent advances in the identification of mouse plasma cells have enabled a more detailed assessment of their development and maintenance to be undertaken. Insertion of the gene encoding green fluorescent protein into the Blimp1 locus has allowed measurement of the efficiency and kinetics with which subsets of mature B cells generate antibody-secreting cells (ASCs) after culture with a series of mitogens, with and without co-stimulation. In vivo identification of plasma cells has allowed their phenotype to be defined and changes in their frequency as a result of aging and immunisation to be monitored. This new approach has allowed also a more precise definition of the genetic program activated in plasma cell differentiation. In this ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500167 Fri, 01 Feb 2008 05:00:00 +0100 1500167 http://www.medworm.com/index.php?rid=1500166&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%3D18243016%26dopt%3DAbstract Authors: Tsuji M, Suzuki K, Kinoshita K, Fagarasan S The gastrointestinal tract is colonized by an immense number of bacteria that are in a constant dialog with our immune cells. One obvious question is how the mucosal immune system maintains a state of hypo-responsiveness toward the commensal bacteria and a state of readiness that allows efficient and prompt responses against pathogens. The answers have important implications for immunologists who seek to understand the fundamental aspects of bacteria-immune cell interactions in the steady-state condition and wish to elucidate the patho-physiologic mechanisms in immune disregulations, such as inflammatory bowel diseases. An important adjustment of the immune system to bacterial colonization of the gut is the "constitutive" production ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500166 Fri, 01 Feb 2008 05:00:00 +0100 1500166 http://www.medworm.com/index.php?rid=1500165&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%3D18243017%26dopt%3DAbstract Authors: Lokmic Z, Lämmermann T, Sixt M, Cardell S, Hallmann R, Sorokin L Until recently little information was available on the molecular details of the extracellular matrix (ECM) of secondary lymphoid tissues. There is now growing evidence that these ECMs are unique structures, combining characteristics of basement membranes and interstitial or fibrillar matrices, resulting in scaffolds that are strong and highly flexible and, in certain secondary lymphoid compartments, also forming conduit networks for rapid fluid transport. This review will address the structural characteristics of the ECM of the murine spleen and its potential role as an organizer of immune cell compartments, with reference to the lymph node where relevant. PMID: 18243017 [PubMed - in process] (Source: Se... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500165 Fri, 01 Feb 2008 05:00:00 +0100 1500165 http://www.medworm.com/index.php?rid=1500164&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%3D18243730%26dopt%3DAbstract Authors: Carter RH, Myers R The germinal center is a critical locus in the production of protective immunity, but its function is poorly understood. Studies of mutant forms of CD19 revealed differences in signaling in different compartments inside the germinal center, and structural findings indicate a selective role in the interaction with follicular dendritic cells in the GC. Loss of these signals leads to surprising changes in germinal center B cells that challenge previous models of GC function. PMID: 18243730 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500164 Fri, 01 Feb 2008 05:00:00 +0100 1500164 http://www.medworm.com/index.php?rid=1500163&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%3D18243731%26dopt%3DAbstract Authors: Carragher DM, Rangel-Moreno J, Randall TD Ectopic or tertiary lymphoid tissues develop at sites of inflammation or infection in peripheral, non-lymphoid organs. These tissues are architecturally similar to conventional secondary lymphoid organs, with separated B and T cell areas, specialized populations of dendritic cells, well-differentiated stromal cells and high endothelial venules. Ectopic lymphoid tissues are often associated with the local pathology that results from chronic infection or chronic inflammation. However, there are also examples in which ectopic lymphoid tissues appear to contribute to local protective immune responses. Here we review how ectopic lymphoid structures develop and function in the context of local immunity and pathology. PMID: 18243731 [PubM... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500163 Fri, 01 Feb 2008 05:00:00 +0100 1500163 http://www.medworm.com/index.php?rid=1500161&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%3D18258454%26dopt%3DAbstract Authors: Sanz I, Wei C, Lee FE, Anolik J Memory B cells are more heterogeneous than previously thought. Given that B cells play powerful antibody-independent effector functions, it seems reasonable to assume division of labor between distinct memory B cells subpopulations in both protective and pathogenic immune responses. Here we review the information emerging regarding the heterogeneity of human memory B cells. A better understanding of this topic should greatly improve our ability to target specific B cell subsets either in vaccine responses or in autoimmune diseases and organ rejection among other pathological conditions where B cells play central pathogenic roles. PMID: 18258454 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500161 Fri, 01 Feb 2008 05:00:00 +0100 1500161 http://www.medworm.com/index.php?rid=1500160&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%3D18261920%26dopt%3DAbstract Authors: Allen CD, Cyster JG Follicular dendritic cells (FDCs) were identified decades ago by their ability to retain immune complexes and more recent findings indicate that they are a source of B cell attractants and trophic factors. New imaging studies have shown that B cells closely associate with their dendritic processes during migration. Here we will review the properties of these specialized follicular stromal cells and provide an update on the requirements for their maturation into phenotypically distinct cells within germinal center light and dark zones. We will then discuss current understanding of how they help support the B cell immune response. PMID: 18261920 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500160 Fri, 01 Feb 2008 05:00:00 +0100 1500160 http://www.medworm.com/index.php?rid=1500159&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%3D18272389%26dopt%3DAbstract Authors: Kearney JF PMID: 18272389 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500159 Fri, 01 Feb 2008 05:00:00 +0100 1500159 http://www.medworm.com/index.php?rid=1500185&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%3D18023589%26dopt%3DAbstract Authors: Stockinger B, Veldhoen M, Martin B While the cytokine IL-17 has been cloned and described more than 10 years ago [Yao Z, Fanslow WC, Seldin MF, Rousseau AM, Painter SL, Comeau MR, et al. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 1995;3(6):811-21; Kennedy J, Rossi DL, Zurawski SM, Vega Jr F, Kastelein RA, Wagner JL, et al. Mouse IL-17: a cytokine preferentially expressed by alpha beta TCR+CD4-CD8-T cells. J Interferon Cytokine Res 1996;16(8):611-7], it was only 2 years ago that IL-17 producing T cells have been classified as a new distinct CD4 T cell subset [Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500185 Sat, 01 Dec 2007 05:00:00 +0100 1500185 http://www.medworm.com/index.php?rid=1500181&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%3D18035554%26dopt%3DAbstract Authors: Korn T, Oukka M, Kuchroo V, Bettelli E Upon activation, naïve CD4(+) T cells differentiate into effector T cells with specific effector functions and cytokine profiles. The Th1/Th2 paradigm has recently been reevaluated to include a third population of T helper cells, producing IL-17 and designated Th17. The differentiation of Th17 cells requires the coordinate and specific action of the proinflammatory cytokine IL-6 and the immunosuppressive cytokine TGF-beta. In addition, the IL-12 family member IL-23 is involved in the maintenance of these cells. Analogous to other T helper cell subsets, Th17 commitment is initiated by sequential involvement of STAT molecules, i.e. STAT3 downstream of cytokine receptors, and specific transcription factors, i.e. ROR-gammat. Recent data ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500181 Sat, 01 Dec 2007 05:00:00 +0100 1500181 http://www.medworm.com/index.php?rid=1500180&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%3D18053739%26dopt%3DAbstract Authors: Ivanov II, Zhou L, Littman DR The paradigm of effector T helper cell differentiation into either Th1 or Th2 lineages has been profoundly shaken by the discovery of T cells that secrete IL-17 and other inflammatory cytokines. This subset, referred to as Th17, is centrally involved in autoimmune disease and is important in host defense at mucosal surfaces. In mouse, a series of cytokines, including IL-6, IL-21, IL-23, and TGF-beta, function sequentially or synergistically to induce the Th17 lineage. Other cytokines, including IL-2, IL-4, IFNgamma, and IL-27, inhibit differentiation of this lineage. Here we review how the nuclear orphan receptor RORgammat functions to coordinate the diverse cytokine-induced signals and thus controls Th17 cell differentiation. PMID: 18053739 [... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500180 Sat, 01 Dec 2007 05:00:00 +0100 1500180 http://www.medworm.com/index.php?rid=1500179&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%3D18054248%26dopt%3DAbstract Authors: Aujla SJ, Dubin PJ, Kolls JK Th17 cells are a new lineage of T-cells that are controlled by the transcription factor RORgammat and develop independent of GATA-3, T-bet, Stat 4 and Stat 6. Novel effector molecules produced by these cells include IL-17A, IL-17F, IL-22, and IL-26. IL-17RA binds IL-17A and IL-17F and is critical for host defense against extracellular planktonic bacteria by regulating chemokine gradients for neutrophil emigration into infected tissue sites as well as host granulopoiesis. Moreover, IL-17 and IL-22 regulate the production of antimicrobial proteins in mucosal epithelium. Although TGF-beta1 and IL-6 have been shown to be critical for development of Th17 cells from naive precursors, IL-23 is also important in regulating IL-17 release in mucosal tissues ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500179 Sat, 01 Dec 2007 05:00:00 +0100 1500179 http://www.medworm.com/index.php?rid=1500176&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%3D18083530%26dopt%3DAbstract Authors: Ghilardi N, Ouyang W T helper (TH) cells can assume different phenotypes characterized by the secretion of distinct effector molecules. Interferon-gamma producing TH1 and IL-4 producing TH2 cells have long been recognized as important mediators of host defense, whereas regulatory T cells are known to suppress T cell responses. Recently, TH17 cells were characterized as a novel CD4(+) subset that preferentially produces IL-17, IL-17F, and IL-22 as the signature cytokines. TH17 cells appear to play a critical role in sustaining the inflammatory response and their presence is closely associated with autoimmune disease, which makes them an attractive therapeutic target. In this review, we focus on the mechanisms that regulate the differentiation of naive T cells into TH17 cells an... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500176 Sat, 01 Dec 2007 05:00:00 +0100 1500176 http://www.medworm.com/index.php?rid=1500172&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%3D18166487%26dopt%3DAbstract Authors: Chen Z, Laurence A, O'Shea JJ The discovery of a new lineage of helper T cells that selectively produces interleukin (IL)-17 has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. Additionally, the discovery of this T cell subset has offered a fresh look at how the complexity of selective regulation of cytokine gene expression might relate to lineage commitment, terminal differentiation and immunologic memory. Information continues to accumulate on factors that regulate Th17 differentiation at a rapid pace and a few lessons have emerged. Like other lineages, Th17 cells preferentially express a transcription factor, retinoic acid-related orphan receptor (ROR)gammat, whose expression seems to be necessary for IL-17 pro... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500172 Sat, 01 Dec 2007 05:00:00 +0100 1500172 http://www.medworm.com/index.php?rid=1500169&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%3D18221887%26dopt%3DAbstract Authors: Stumhofer JS, Silver J, Hunter CA The discovery of the Th17 lineage of T helper cells and the realization that this subset was implicated in the pathogenesis of a variety of inflammatory conditions has lead to an intense effort devoted to identifying the cytokines and transcription factors that promote their development. In contrast, less attention has been paid to understanding the cytokines that temper Th17 activity. Recent studies, however, have provided insights into the cytokines that limit these T cells. The aim of this article is to review our current understanding of the regulatory networks that limit T helper subsets and how they relate to the Th17 lineage. PMID: 18221887 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500169 Sat, 01 Dec 2007 05:00:00 +0100 1500169 http://www.medworm.com/index.php?rid=1500158&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%3D18276155%26dopt%3DAbstract Authors: Weaver CT, Murphy KM PMID: 18276155 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500158 Sat, 01 Dec 2007 05:00:00 +0100 1500158 http://www.medworm.com/index.php?rid=1500157&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%3D18319054%26dopt%3DAbstract Authors: McGeachy MJ, Cua DJ IL-23--produced by dendritic cells--and Th17 cells have both been identified as major factors involved in autoimmune inflammation, yet their relationship with each other remains controversial. This review aims to describe the initial discovery of Th17 cells, their subsequent characterization as a unique T helper subset in mouse and man, as well as the mechanisms involved in regulating these cells. Finally, the roles of IL-23 in inflammatory diseases in relation to Th17 function will be discussed. PMID: 18319054 [PubMed - in process] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500157 Sat, 01 Dec 2007 05:00:00 +0100 1500157 http://www.medworm.com/index.php?rid=1500177&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%3D18060803%26dopt%3DAbstract Authors: Zúñiga-Pflücker JC, van den Brink MR PMID: 18060803 [PubMed - as supplied by publisher] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500177 Wed, 28 Nov 2007 05:00:00 +0100 1500177 http://www.medworm.com/index.php?rid=1500190&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%3D17964803%26dopt%3DAbstract Authors: Goldberg GL, Zakrzewski JL, Perales MA, van den Brink MR Strategies to enhance T cell recovery are of increasing clinical importance to overcome long lasting T cell deficiencies, which occur in association with infections, autoimmunity and chemo/radiotherapy as well as aging of the immune system. In this review we discuss those strategies that are close to or in the clinic. Interleukin-7, sex steroid modulation, keratinocyte growth factor, growth hormone and cellular therapies using ex vivo generated T-cell precursors are currently being tested in recipients of a hematopoietic stem cell transplantation and patients with malignancies or HIV/AIDS. PMID: 17964803 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500190 Mon, 01 Oct 2007 04:00:00 +0100 1500190 http://www.medworm.com/index.php?rid=1500189&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%3D17997107%26dopt%3DAbstract Authors: Legrand N, Dontje W, van Lent AU, Spits H, Blom B The thymus supports the development of T cells throughout life from hematopoietic progenitor cells migrating from the bone marrow. During the early years after birth thymic activity is highest, but progressively declines resulting in diminished naïve T cell output. Underlying causes of thymic involution may be degeneration of the stromal thymic network, providing survival and differentiation factors for developing T cells, or insufficiency of the progenitor cells to home and/or develop in the aged thymus. In young people the reduced thymic output is insignificant, since the peripheral T cell compartment is under compensatory homeostatic control. However, in more or less immunocompromised individuals, including aged people ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500189 Mon, 01 Oct 2007 04:00:00 +0100 1500189 http://www.medworm.com/index.php?rid=1500188&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%3D17997108%26dopt%3DAbstract Authors: Awong G, La Motte-Mohs RN, Zúñiga-Pflücker JC Immunodeficient individuals are susceptible to opportunistic infection. While stem cell transplantation can restore a functional immune system, T cells are slow to recover and limited in eliciting adaptive immune responses. Approaches to selectively enhance T cell function have focused on boosting thymopoiesis to generate new T cells or expanding existing T cells. By taking advantage of the role of Notch signaling in T cell development, we have developed an in vitro system able to generate large numbers of progenitor T cells from human hematopoietic stem cells. Here, we discuss this in vitro system and its implications for the potential treatment of T cell immunodeficiency. PMID: 17997108 [PubMed - indexed for ME... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500188 Mon, 01 Oct 2007 04:00:00 +0100 1500188 http://www.medworm.com/index.php?rid=1500187&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%3D18023361%26dopt%3DAbstract Authors: Williams KM, Hakim FT, Gress RE T cell reconstitution following lymphopenia from chemotherapy or stem cell transplant is often slow and incompetent, contributing to the development of infectious diseases, relapse, and graft-versus-host disease. This is due to the fact that de novo T cell production is impaired following cytoreductive regimens. T cells can be generated from two pathways: (1) thymus derived through active thymopoiesis and (2) peripherally expanded clones through homeostatic proliferation. During recovery from lymphopenia, the thymic pathway is commonly compromised in adults and T cells rely upon peripheral expansion to restore T cell numbers. This homeostatic proliferation exploits the high cytokine levels following lymphopenia to rapidly generate T cells in the... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500187 Mon, 01 Oct 2007 04:00:00 +0100 1500187 http://www.medworm.com/index.php?rid=1500186&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%3D18023362%26dopt%3DAbstract This article will summarize our current knowledge on this topic and will discuss future research directions as well as the potential and power of translational studies in non-human primate models of infection, aging and bone marrow transplantation. PMID: 18023362 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500186 Mon, 01 Oct 2007 04:00:00 +0100 1500186 http://www.medworm.com/index.php?rid=1500184&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%3D18024073%26dopt%3DAbstract Authors: Chidgey A, Dudakov J, Seach N, Boyd R The immune system undergoes dramatic changes with age-the thymus involutes, particularly from puberty, with the gradual loss of newly produced naïve T cells resulting in a restricted T cell receptor repertoire, skewed towards memory cells. Coupled with a similar, though less dramatic age-linked decline in bone marrow function, this translates to a reduction in immune responsiveness and has important clinical implications particularly in immune reconstitution following cytoablation regimes for cancer treatment or following severe viral infections such as HIV. Given that long-term reconstitution of the immune system is dependent on the bi-directional interplay between primary lymphoid organ stromal cells and the progenitors whose downst... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500184 Mon, 01 Oct 2007 04:00:00 +0100 1500184 http://www.medworm.com/index.php?rid=1500182&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%3D18035553%26dopt%3DAbstract Authors: Hudson LL, Louise Markert M, Devlin BH, Haynes BF, Sempowski GD The thymus is essential for proper development and maintenance of a broad T cell repertoire capable of recognizing a wide-range of foreign antigens. Recent advances in multicolor flow cytometry, non-invasive imaging techniques, and molecular assessments of thymic function have enabled a more comprehensive characterization of human thymic output in clinical settings than in the past. These techniques have been particularly valuable in monitoring human T cells after therapeutic thymic grafting for complete DiGeorge syndrome and during HIV-1 infection and AIDS. By defining the degree and mechanisms of T cell reconstitution in these settings, clinical investigators and primary caregivers have been able to better diagn... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500182 Mon, 01 Oct 2007 04:00:00 +0100 1500182 http://www.medworm.com/index.php?rid=1500202&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%3D17398113%26dopt%3DAbstract Authors: Irvine DJ, Doh J T cell activation occurs when T cell receptors engage peptide-major histocompatibility complex (pMHC) molecules displayed on the surface of antigen presenting cells (APCs). Clustering of TCRs and other receptors in physical patterns at the T-APC interface forms a structure known as an immunological synapse (IS). Studies of the IS are challenging due to the cell-cell contact context of the governing interactions. Model surfaces as synthetic APCs have thus been developed, where the type, quantity, and physical arrangement of ligands displayed to T cells are precisely controlled. These model systems have provided important insights into the structure and function of the IS. PMID: 17398113 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500202 Wed, 01 Aug 2007 04:00:00 +0100 1500202 http://www.medworm.com/index.php?rid=1500201&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%3D17398114%26dopt%3DAbstract Authors: Wucherpfennig KW, Allen PM, Celada F, Cohen IR, De Boer R, Garcia KC, Goldstein B, Greenspan R, Hafler D, Hodgkin P, Huseby ES, Krakauer DC, Nemazee D, Perelson AS, Pinilla C, Strong RK, Sercarz EE A recent workshop discussed the recognition of multiple distinct ligands by individual T cell and B cell receptors and the implications of this discovery for lymphocyte biology. The workshop recommends general use of the term polyspecificity because it emphasizes two fundamental aspects, the inherent specificity of receptor recognition and the ability to recognize multiple ligands. Many different examples of polyspecificity and the structural mechanisms were discussed, and the group concluded that polyspecificity is a general, inherent feature of TCR and antibody recognition. This r... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500201 Wed, 01 Aug 2007 04:00:00 +0100 1500201 http://www.medworm.com/index.php?rid=1500197&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%3D17434316%26dopt%3DAbstract Authors: Korn T, Oukka M Naturally occurring regulatory T-cells (nT-reg) are crucial in preventing generalized autoimmunity. However, antigen-specific T-reg responses during organ-specific autoimmunity have not been characterized until recently when novel tools including MHC class II-tetramers and Foxp3gfp "knock-in" reporter mice (Foxp3gfp.KI) became available. In this review, we introduce the concept of functional compartmentalisation in that T-reg may behave differently when they maintain peripheral tolerance in the secondary lymphoid tissue in a non-inflammatory environment as compared to when they are expanded and targeted to the site of inflammation following an autoantigen-specific, immunogenic stimulus. PMID: 17434316 [PubMed - indexed for MEDLINE] (Source: Seminars in Immu... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500197 Wed, 01 Aug 2007 04:00:00 +0100 1500197 http://www.medworm.com/index.php?rid=1500194&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%3D17521918%26dopt%3DAbstract Authors: Mazza C, Malissen B MHC-encoded molecules govern adaptive immune responses by presenting peptides to T cell receptors (TCRs). Based on TCR-MHC crystal structures, we revisit the extent of TCR binding degeneracy, a property with important biological consequences because the diversity of TCR ligands that can be encountered exceeds the number of T cell clones present in a person at any one time. We also discuss whether the approximate diagonal binding of TCR on MHC molecules is due to an intrinsic property of the TCR variable regions, or results from the action of the CD4 and CD8 coreceptors during intrathymic T cell selection. Finally, we discuss how MHC restriction of antigen recognition might have emerged during evolution. PMID: 17521918 [PubMed - indexed for MEDLINE] (Sou... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500194 Wed, 01 Aug 2007 04:00:00 +0100 1500194 http://www.medworm.com/index.php?rid=1500193&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%3D17548210%26dopt%3DAbstract Authors: Krogsgaard M, Juang J, Davis MM The mechanisms by which alphabeta T-cells are selected in the thymus and then recognize peptide MHC (pMHC) complexes in the periphery remain an enigma. Recent work particularly with respect to quantification of T-cell sensitivity and the role of self-ligands in T-cell activation has provided some important clues to the details of how TCR signaling might be initiated. Here, we highlight recent experimental data that provides insights into the initiation of T-cell activation and also discuss the main controversies and uncertainties in this area. PMID: 17548210 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500193 Wed, 01 Aug 2007 04:00:00 +0100 1500193 http://www.medworm.com/index.php?rid=1500192&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%3D17560120%26dopt%3DAbstract Authors: Sundberg EJ, Deng L, Mariuzza RA Major histocompatibility complex (MHC) class II molecules display peptides to the T cell receptor (TCR). The ability of the TCR to discriminate foreign from self-peptides presented by MHC molecules is a requirement of an effective adaptive immune response. Dysregulation of this molecular recognition event often leads to a disease state. Recently, a number of structural studies have provided significant insight into several such dysregulated interactions between peptide/MHC complexes and TCR molecules. These include TCR recognition of self-peptides, which results in autoimmune reactions, and of mutant self-peptides, common in the immunosurveillance of tumors, as well as the engagement of TCRs by superantigens, a family of bacterial toxins respon... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500192 Wed, 01 Aug 2007 04:00:00 +0100 1500192 http://www.medworm.com/index.php?rid=1500191&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%3D17560121%26dopt%3DAbstract Authors: Choudhuri K, van der Merwe PA Despite intensive investigation we still do not understand how the T cell antigen receptor (TCR) tranduces signals across the plasma membrane, a process referred to as TCR triggering. Three basic mechanisms have been proposed, involving aggregation, conformational change, or segregation of the TCR upon binding pMHC ligand. Given the low density of pMHC ligand it remains doubtful that TCR aggregation initiates triggering, although it is likely to enhance subsequent signalling. Structural studies to date have not provided definitive evidence for or against a conformational change mechanism, but they have ruled out certain types of conformational change. Size-induced segregation of the bound TCR from inhibitory membrane tyrosine phosphatases seems to... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500191 Wed, 01 Aug 2007 04:00:00 +0100 1500191 http://www.medworm.com/index.php?rid=1500207&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%3D17382557%26dopt%3DAbstract Authors: Mescher MF, Agarwal P, Casey KA, Hammerbeck CD, Xiao Z, Curtsinger JM CD8 T cells specific for self-antigens are present in the peripheral lymphoid system and can contribute to autoimmunity or transplant rejection. Whether recognition of Ag leads to full activation, or to induction of tolerance, depends upon availability of cytokine at critical stages of the response. Signals provided by IL-12 and/or IFN-alpha/beta are required for activation of naïve CD8 T cells, and IL-2 is needed to sustain and further expand the effector cells if Ag persists. These critical signaling requirements provide new insights into the factors that regulate the CD8 T cell contributions to development of autoimmunity or rejection of transplants. PMID: 17382557 [PubMed - indexed for MEDLINE] ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500207 Fri, 01 Jun 2007 04:00:00 +0100 1500207 http://www.medworm.com/index.php?rid=1500206&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%3D17383195%26dopt%3DAbstract Authors: Wells AD A large body of research has established the importance of costimulatory signals and proliferation for the generation of productive T cell immune responses. While costimulation and cell cycle progression are each individually necessary for CD4+ effector T cell differentiation, it has become clear that neither of these processes alone is sufficient to avoid anergy. This review outlines the links between T cell differentiation, tolerance, and the cell cycle, and highlights recent work that has implicated cyclin-dependent kinases as important regulators and potential targets for modulation of T cell immunity and tolerance. PMID: 17383195 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500206 Fri, 01 Jun 2007 04:00:00 +0100 1500206 http://www.medworm.com/index.php?rid=1500205&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%3D17383196%26dopt%3DAbstract Authors: Mondino A, Mueller DL Several events control the activation, proliferation, and the continued Ag responsiveness of naïve and memory T lymphocytes. Here we review the individual contributions of TCR, CD28, and IL-2-driven signaling to T cell proliferation and anergy avoidance. The role of mTOR as a rheostat capable of integrating extracellular, plasma membrane-associated, and intracellular signals with relevance to T cell priming and tolerance is discussed. PMID: 17383196 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500205 Fri, 01 Jun 2007 04:00:00 +0100 1500205 http://www.medworm.com/index.php?rid=1500204&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%3D17387022%26dopt%3DAbstract Authors: Bandyopadhyay S, Soto-Nieves N, Macián F Self-reactive T cells that escape negative selection in the thymus must be kept under control in the periphery. Mechanisms of peripheral tolerance include deletion or functional inactivation of self-reactive T cells and mechanisms of dominant tolerance mediated by regulatory T cells. In the absence of costimulation, T cell receptor (TCR) engagement results in unopposed calcium signaling that leads to the activation of a cell-intrinsic program of inactivation, which makes T cells hyporesponsive to subsequent stimulations. The activation of this program in anergic T cells is a consequence of the induction of a nuclear factor of activated T cells (NFAT)-dependent program of gene expression. Recent studies have offered new insights int... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500204 Fri, 01 Jun 2007 04:00:00 +0100 1500204 http://www.medworm.com/index.php?rid=1500203&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%3D17391982%26dopt%3DAbstract Authors: Loeser S, Penninger JM The family of the Casitas B-lineage Lymphoma (Cbl) proteins, c-Cbl, Cbl-b, and Cbl-3, function as E3 ubiquitin ligases and molecular adaptors. In particular, Cbl-b acts as a gatekeeper in T cell activation that controls activation thresholds and the requirement for co-stimulation. Loss of Cbl-b expression renders animals susceptible to antigen-triggered autoimmunity suggesting that Cbl-b is a key autoimmunity gene. In addition, Cbl-b plays a critical role in T cell anergy and escape from regulatory T cells (Treg) suppression. Modulation of Cbl-b might provide us with a unique opportunity for future immune treatment of human disorders such as autoimmunity, immunodeficiency, or cancer. PMID: 17391982 [PubMed - indexed for MEDLINE] (Source: Seminars in ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500203 Fri, 01 Jun 2007 04:00:00 +0100 1500203 http://www.medworm.com/index.php?rid=1500200&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%3D17400472%26dopt%3DAbstract Authors: Choi S, Schwartz RH Since the original description of T cell anergy in CD4 clones from mice and humans, a number of different unresponsive states have been described, both in vivo and in vitro, that have been called anergic. While initial attempts were made to understand the similarities between the different models, it has now become clear from biochemical experiments that many of them have different molecular mechanisms underlying their unresponsiveness. In this review we will detail our own work on the in vivo model referred to as adaptive tolerance and then attempt to compare this biochemical state to the multitude of other states that have been described in the literature. PMID: 17400472 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500200 Fri, 01 Jun 2007 04:00:00 +0100 1500200 http://www.medworm.com/index.php?rid=1500199&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%3D17403607%26dopt%3DAbstract Authors: Schartner JM, Fathman CG, Seroogy CM Until recently ubiquitination of a protein was thought to simply serve the mundane task of targeting a protein for proteasomal degradation. Accumulating evidence over the past decade has demonstrated the importance of ubiquitination in non-degradative functions including regulating cellular signaling, that highlight its role in human disease and thus potential development of novel therapeutics. Much has been written about ubiquitination in the immune system, in this review we will outline our current knowledge of ubiquitination with respect to T cell tolerance. Specifically, we will provide on overview of E3 ubiquitin ligases and their role in various states of CD4+ T cell tolerance: central and peripheral. PMID: 17403607 [PubMed - inde... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500199 Fri, 01 Jun 2007 04:00:00 +0100 1500199 http://www.medworm.com/index.php?rid=1500198&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%3D17433711%26dopt%3DAbstract Authors: Liu YC Tagging a small molecule ubiquitin to a protein substrate, or protein ubiquitination, plays an important role in the immune responses. This process is catalyzed by a cascade of enzymatic reactions, with the E3 ubiquitin ligases being the critical enzymes that determine the specificity of substrate recognition. The E3 ligase Itch was identified from a mutant mouse which displays skin scratching and abnormal immune disorders. In the past few years, much progress has been made in our understanding of Itch-promoted protein ubiquitination, modulation of its ligase activity by upstream kinases, and the kinase-ligase interaction in T cell differentiation and tolerance induction. PMID: 17433711 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500198 Fri, 01 Jun 2007 04:00:00 +0100 1500198 http://www.medworm.com/index.php?rid=1500219&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%3D17035042%26dopt%3DAbstract This article summarizes current bacteriological knowledge of the community and highlights topics of potential interest to innovative immunologists. The role of the bacterial community in the development and regulation of the immune system of neonates seems likely to be a particularly important area of future research. PMID: 17035042 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500219 Sun, 01 Apr 2007 04:00:00 +0100 1500219 http://www.medworm.com/index.php?rid=1500218&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%3D17055292%26dopt%3DAbstract Authors: Schenk M, Mueller C Intestinal macrophages, preferentially located in the subepithelial lamina propria, represent in humans the largest pool of tissue macrophages. To comply with their main task, i.e. the efficient removal of microbes and particulate matter that might have gained access to the mucosa from the intestinal lumen while maintaining local tissue homeostasis, several phenotypic and functional adaptations evolved. Most notably, microbe-associated molecular pattern (MAMP) receptors, including the lipopolysaccharide receptors CD14 and TLR4, but also the Fc receptors for IgA and IgG are absent on most intestinal Mø. Here we review recent findings on the phenotypic and functional adaptations of intestinal Mø and their implications for the pathogenesis of inflamm... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500218 Sun, 01 Apr 2007 04:00:00 +0100 1500218 http://www.medworm.com/index.php?rid=1500217&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%3D17118672%26dopt%3DAbstract Authors: Smith K, McCoy KD, Macpherson AJ Vertebrates are essentially born germ-free but normally acquire a complex intestinal microbiota soon after birth. Most of these organisms are non-pathogenic to immunocompetent hosts; in fact, many are beneficial, supplying vitamins for host nutrition and filling the available microbiological niche to limit access and consequent pathology when pathogens are encountered. Thus, mammalian health depends on mutualism between host and flora. This is evident in inflammatory conditions such as inflammatory bowel disease, where aberrant responses to microbiota can result in host pathology. Studies with axenic (germ-free) or deliberately colonised animals have revealed that commensal organisms are required for the development of a fully functional immune... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500217 Sun, 01 Apr 2007 04:00:00 +0100 1500217 http://www.medworm.com/index.php?rid=1500216&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%3D17161619%26dopt%3DAbstract Authors: Suzuki K, Ha SA, Tsuji M, Fagarasan S Our intestine is colonized by an impressive community of bacteria, that has profound effects on the immune functions. The relationship between gut microbiota and the immune system is one of reciprocity: bacteria have important contribution in nutrient processing and education of the immune system and conversely, the immune system, particularly gut-associated lymphoid tissues (GALT) plays a key role in shaping the repertoire of gut microbiota. In this review we discuss new insights into the role of IgA in the maintenance of immune homeostasis and the reciprocal interactions between gut B cells and intestinal bacteria. PMID: 17161619 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500216 Sun, 01 Apr 2007 04:00:00 +0100 1500216 http://www.medworm.com/index.php?rid=1500210&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%3D17320411%26dopt%3DAbstract Authors: Coombes JL, Maloy KJ Many different pathways contribute to the maintenance of tolerance to harmless antigens in the intestine. When these important pathways are compromised, chronic intestinal inflammation can develop. In particular, naturally occurring CD4+CD25+ regulatory T cells have been shown to play an important role in the prevention and cure of colitis in animal models of intestinal inflammation. These regulatory T cell responses may be influenced by the local environment in the intestine. For example, functionally specialised populations of dendritic cells exist in the intestine which may favour regulatory type responses. Understanding how these pathways intersect may lead to the development of more specific therapies for the treatment of inflammatory bowel disease. ... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500210 Sun, 01 Apr 2007 04:00:00 +0100 1500210 http://www.medworm.com/index.php?rid=1500209&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%3D17324587%26dopt%3DAbstract Authors: Magalhaes JG, Tattoli I, Girardin SE The gastrointestinal tract is fundamental for the uptake of nutrients and fluids, but it also represents the greatest surface of the body in contact with the external environment and most human pathogens enter the body through the mucosal surface, especially in the intestine. The intestinal immune system protects the sterile core of the organism against invasion and systemic dissemination of both pathogens and limits for level penetration of commensal microorganisms. In addition, the human intestine is continually in contact with 10(14) commensal bacteria containing more than 500 different species. These commensal bacteria confer health benefits to their host by helping dietary digestion, development of gut immunity and preventing colonizat... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500209 Sun, 01 Apr 2007 04:00:00 +0100 1500209 http://www.medworm.com/index.php?rid=1500196&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%3D17485224%26dopt%3DAbstract Authors: Salzman NH, Underwood MA, Bevins CL Mucosal surfaces are colonized by a diverse and dynamic microbiota. Much investigation has focused on bacterial colonization of the intestine, home to the vast majority of this microbiota. Experimental evidence has highlighted that these colonizing microbes are essential to host development and homeostasis, but less is known about host factors that may regulate the composition of this ecosystem. While evidence shows that IgA has a role in shaping this microbiota, it is likely that effector molecules of the innate immune system are also involved. One hypothesis is that gene-encoded antimicrobial peptides, key elements of innate immunity throughout nature, have an essential role in this regulation. These effector molecules characteristically h... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500196 Sun, 01 Apr 2007 04:00:00 +0100 1500196 http://www.medworm.com/index.php?rid=1500195&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%3D17499514%26dopt%3DAbstract Authors: Macpherson AJ, Hapfelmeier S, McCoy KD PMID: 17499514 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500195 Sun, 01 Apr 2007 04:00:00 +0100 1500195 http://www.medworm.com/index.php?rid=1500215&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%3D17275323%26dopt%3DAbstract Authors: Kawai T, Akira S The TLR family senses the molecular signatures of microbial pathogens, and plays a fundamental role in innate immune responses. TLRs signal via a common pathway that leads to the expression of diverse inflammatory genes. In addition, each TLR elicits specific cellular responses to pathogens owing to differential usage of intracellular adapter proteins. Recent studies have revealed the importance of the subcellular localization of TLRs in pathogen recognition and signaling. TLR signaling pathways is negatively regulated by a number of cellular proteins to attenuate inflammation. Here, we describe recent advances in our understanding of the regulation of TLR-mediated signaling. PMID: 17275323 [PubMed - indexed for MEDLINE] (Source: Seminars in Immunology) Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500215 Thu, 01 Feb 2007 05:00:00 +0100 1500215 http://www.medworm.com/index.php?rid=1500214&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%3D17275324%26dopt%3DAbstract Authors: Miyake K The Toll family of receptors consists of cell surface TLRs (TLR4/MD-2, TLR1, TLR2, and TLR6) and intracellular TLRs (TLR3, TLR7, TLR8, and TLR9). Cell surface TLRs sense microbial membranes such as lipopolysaccharide or lipopeptides. Recognition by TLRs is the frontline where pathogens and a host try to take the control of immune responses. Bacteria can modulate the structure of a TLR ligand lipid A to subvert host responses. Cell surface TLRs also sense endogenous ligands which are released in tissue damages as danger signals and induce inflammation in infectious and non-infectious condition. The availability of endogenous ligands and the amount of cell surface TLRs are both tightly limited to keep TLR responses sufficient for containment of pathogens without detrime... Seminars in Immunology journals http://www.medworm.com/rss/comments.php?id=1500214 Thu, 01 Feb 2007 05:00:00 +0100 1500214