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 'European Journal of Immunology' source. Fri, 19 Mar 2010 13:40:18 +0100 http://www.medworm.com/index.php?rid=3374734&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20232340%26dopt%3DAbstract Authors: Trembleau S, Hoffmann M, Meyer B, Nell V, Radner H, Zauner W, Hammer J, Aichinger G, Fischer G, Smolen J, Steiner G The heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been described as important autoantigen in rheumatoid arthritis (RA) since it is targeted by autoantibodies, autoreactive T cells, and is aberrantly expressed in synovial cells in patients. To identify hnRNP-A2-specific T cell epitopes possibly associated with pathogenicity, we used an innovative approach. We first scanned 280 overlapping hnRNP-A2 peptides for binding to the RA-associated class II molecules HLA-DR4 and HLA-DR1, leading to a comprehensive selection of binders. The finally selected peptides were tested in IFN-gamma-specific ELISPOT assay: PBMC from 18% of RA patients showed a significant... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3374734 Mon, 15 Mar 2010 00:00:00 +0100 3374734 http://www.medworm.com/index.php?rid=3374733&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20232341%26dopt%3DAbstract Authors: Guerreiro M, Na IK, Letsch A, Haase D, Bauer S, Meisel C, Roemhild A, Reinke P, Volk HD, Scheibenbogen C Epstein-Barr virus (EBV) infection leads to life-long viral persistence. Although EBV infection can result in chronic disease and malignant transformation, most carriers remain disease-free as a result of effective control by T cells. EBV-specific IFN-gamma-producing T cells could be demonstrated in acute and chronic infection as well as during latency. Recent studies provide, however, evidence that assessing IFN-gamma alone is insufficient to assess the quantity and quality of a T-cell response. Using overlapping peptide pools of latent EBNA-1 and lytic BZLF-1 protein and multicolor flow cytometry, we demonstrate that the majority of ex vivo EBV-reactive T cells in healthy... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3374733 Mon, 15 Mar 2010 00:00:00 +0100 3374733 http://www.medworm.com/index.php?rid=3364283&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939782 In this study, we showed that immature viable DC have the ability to uptake apoptotic DC as well as necrotic DC without it being recognized as an inflammatory event by immature viable DC. However, the specific uptake of apoptotic DC converted immature viable DC into tolerogenic DC, which were resistant to LPS-induced maturation. These tolerogenic DC secreted increased levels of TGF-[beta]1, which induced differentiation of naïve T cells into Foxp3+ Treg. Furthermore, induction of Treg differentiation only occurred upon uptake of apoptotic DC and not apoptotic splenocytes by viable DC, indicating that it is specifically the uptake of apoptotic DC that gives viable immature DC the potential to induce Foxp3+ Treg. Taken together, these findings identify uptake of apoptotic DC by viable immat... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3364283 Mon, 15 Mar 2010 00:00:00 +0100 3364283 http://www.medworm.com/index.php?rid=3363024&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20222088%26dopt%3DAbstract Authors: Day TA, Koch M, Nouailles G, Jacobsen M, Kosmiadi GA, Miekley D, Kuhlmann S, Jörg S, Gamradt P, Mollenkopf HJ, Hurwitz R, Reece ST, Kaufmann SH, Kursar M Tuberculosis (TB) causes 2 million deaths per year, yet in most cases the immune response successfully contains the infection and prevents disease outbreak. Induced lymphoid structures associated with pulmonary granuloma are observed during TB in both humans and mice and could orchestrate host defense. To investigate whether granuloma perform lymphoid functions, mice lacking secondary lymphoid organs (SLO), were infected with Mycobacterium tuberculosis (MTB). As in wild-type mice, granuloma developed, exponential growth of MTB was controlled, and antigen-specific T-cell responses including memory T cells were generated i... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3363024 Wed, 10 Mar 2010 00:00:00 +0100 3363024 http://www.medworm.com/index.php?rid=3355250&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20217862%26dopt%3DAbstract This study documents the existence of a large TCR repertoire specific for the MELOE-1/A2 epitope and its capacity to give rise to antitumor CTL that supports the development of immunotherapies targeting this epitope. PMID: 20217862 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3355250 Tue, 09 Mar 2010 00:00:00 +0100 3355250 http://www.medworm.com/index.php?rid=3347560&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20213733%26dopt%3DAbstract Authors: Trobaugh DW, Yang L, Ennis FA, Green S Memory cross-reactive CD8(+) T cell responses may induce protection or immunopathology upon secondary viral challenge. To elucidate the potential role of T cells in sequential flavivirus infection, we characterized cross-reactive CD4(+) and CD8(+) T cell responses between attenuated and pathogenic Japanese encephalitis virus (JEV) and pathogenic West Nile virus (WNV). A previously reported WNV NS4b CD8(+) T cell epitope and its JEV variant elicited CD8(+) T cell responses in both JEV- and WNV-infected mice. The peptide variant homologous to the immunizing virus induced greater cytokine secretion and activated higher frequencies of epitope-specific CD8(+) T cells. However, there was a virus-dependent, peptide variant-independent pattern of... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3347560 Mon, 08 Mar 2010 00:00:00 +0100 3347560 http://www.medworm.com/index.php?rid=3347559&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20213734%26dopt%3DAbstract Authors: Deak E, Jayakumar A, Cho KW, Goldsmith-Pestana K, Dondji B, Lambris JD, McMahon-Pratt D In visceral leishmaniasis, the draining lymph node (DLN) is the initial site for colonization and establishment of infection after intradermal transmission by the sand fly vector; however, little is known about the developing immune response within this site. Using an intradermal infection model, which allows for parasite visceralization, we have examined the ongoing immune responses in the DLN of BALB/c mice infected with L. infantum. Although not unexpected, at early times post-infection there is a marked B cell expansion in the DLN, which persists throughout infection. However, the characteristics of this response were of interest; as early as day 7 post-infection, polyclonal antibodies ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3347559 Mon, 08 Mar 2010 00:00:00 +0100 3347559 http://www.medworm.com/index.php?rid=3347558&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20213735%26dopt%3DAbstract Authors: Prajeeth CK, Jirmo AC, Krishnaswamy JK, Ebensen T, Guzman CA, Weiss S, Constabel H, Schmidt RE, Behrens GM The property of dendritic cells (DC) to generate effective cytotoxic T lymphocyte (CTL) responses is influenced by Toll-like Receptor (TLR) signalling. TLR ligands contain molecular signatures associated with pathogens, are being exploited as potential adjuvants, and have impact on the antigen processing and presentation by DC. We hypothesized that the TLR2/6 heterodimer agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxyl polyethylene glycol (BPP), a synthetic derivative of the Mycoplasma macrophage activating lipopeptide (MALP-2), is a potent adjuvant for cross-priming against cellular antigens. Systemic administration of BPP induced maturation of... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3347558 Mon, 08 Mar 2010 00:00:00 +0100 3347558 http://www.medworm.com/index.php?rid=3347557&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20213736%26dopt%3DAbstract Authors: Haeberlein S, Sebald H, Bogdan C, Schleicher U Activation of NK cells is a hallmark of infections with intracellular pathogens. We previously showed that the protozoan parasite Leishmania infantum triggered a rapid NK cell response in mice that required TLR9-positive myeloid DC and IL-12, but no IFN-alpha/beta. Here, we investigated whether IL-15 or IL-18 mediate the activity of IL-12 or function as independent activators of NK cells. In contrast to earlier studies that described IL-15 as crucial for NK cell priming in response to TLR ligands, the expression of IFN-gamma, FasL, perforin and granzyme B by NK cells in L. infantum-infected mice was completely preserved in the absence of IL-15, whereas the proliferative capacity of NK cells was lower than in WT mice. IFN-gamma sec... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3347557 Mon, 08 Mar 2010 00:00:00 +0100 3347557 http://www.medworm.com/index.php?rid=3347556&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20213737%26dopt%3DAbstract Authors: Paramita B, Elizabeth S, Dumitriu IE, Katy D, David C, Caroline A, Julian DP, Chai JG, Terence CH, Diane S, Marina B Complement activation is known to have deleterious effects on organ transplantation. On the other hand the complement system is also known to have an important role in regulating immune responses. The balance between these two opposing effects is critical in the context of transplantation. Here, we report that female mice deficient in C1q (C1qa(-/-)) or C3 (C3(-/-)) reject male syngeneic grafts (HY incompatible) at an accelerated rate compared with WT mice. Intranasal HY peptide administration, which induces tolerance to syngeneic male grafts in WT mice, fails to induce tolerance in C1qa(-/-) or C3(-/-) mice. The rejection of the male grafts correlated with the ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3347556 Mon, 08 Mar 2010 00:00:00 +0100 3347556 http://www.medworm.com/index.php?rid=3347555&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20213738%26dopt%3DAbstract Authors: Yamaguchi H, Fujimoto T, Nakamura S, Ohmura K, Mimori T, Matsuda F, Nagata S Milk fat globule EGF factor 8 (MFG-E8) promotes the phagocytosis of apoptotic cells by serving as a bridging molecule between apoptotic cells and phagocytes. Many apoptotic cells are left unengulfed in the germinal centers of the spleen of MFG-E8(-/-) mice, which develop a human systemic lupus erythematosus (SLE)-like autoimmune disease. Here, we analyzed the MFG-E8 gene in human SLE patients, and found in two out of 322 female patients a heterozygous intronic mutation, which caused a cryptic exon from intron 6 to be included in the transcript. The cryptic exon contained a premature termination codon, generating a C-terminally truncated MFG-E8 protein. The mutant MFG-E8 was aberrantly glycosylated and... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3347555 Mon, 08 Mar 2010 00:00:00 +0100 3347555 http://www.medworm.com/index.php?rid=3347561&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20209503%26dopt%3DAbstract Authors: Lee SH, Biron CA The conclusive evidence supporting a role for natural killer (NK) cells in defense against viruses has been obtained under conditions of NK cell deficiencies prior to infections. NK cell proliferation can be induced during infections, but the advantages of resulting expansion have been unclear because NK cell basal frequency is already high. However, NK cell decreases are also observed during certain conditions of viral infection. Given the range of potent antiviral and immunoregulatory functions of NK cells, such "disappearance" dramatically changes the resources available to the host. New studies demonstrate that proliferation dependent on activating receptors for virus-induced ligands is key for NK cell maintenance, and allows their continued availability f... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3347561 Fri, 05 Mar 2010 00:00:00 +0100 3347561 http://www.medworm.com/index.php?rid=3332318&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939419 Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL-7-receptor-[alpha] chain and a unique TSLP receptor (TSLPR) chain. The role of TSLP in human B-cell development has not been elucidated. We show that TSLPR transcripts are expressed most prominently in CD34+ cells from fetal liver and BM. In general, cell surface expression of TSLPR was low, except on a subset of multilineage-commited progenitor cells. TSLP induced the tyrosine-phosphorylation of STAT5 and the proliferation of multilineage-commited progenitor cells, pro-B cells and pre-B cells. Compared with IL-7, the levels of proliferation after stimulation of the B-cell progenitors with TSLP were lower. Expression of the BCR on the cell surface of fetal cells was inversely correlated to TSLP or IL-7 responsiveness. Pre-... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3332318 Fri, 05 Mar 2010 00:00:00 +0100 3332318 http://www.medworm.com/index.php?rid=3338556&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201006%26dopt%3DAbstract Authors: PMID: 20201006 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338556 Wed, 03 Mar 2010 00:00:00 +0100 3338556 http://www.medworm.com/index.php?rid=3338555&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201007%26dopt%3DAbstract Authors: Fitzgerald KA PMID: 20201007 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338555 Wed, 03 Mar 2010 00:00:00 +0100 3338555 http://www.medworm.com/index.php?rid=3338554&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201008%26dopt%3DAbstract Authors: Dinarello CA Although there has been a great amount of progress in the 25 years since the first reporting of the cDNA for IL-1alpha and IL-1beta, the history of IL-1 goes back to the early 1940s. In fact, the entire field of inflammatory cytokines, TLR and the innate immune response can be found in the story of IL-1. This Viewpoint follows the steps from the identification of the fever-inducing activities of "soluble factors" produced by endotoxin-stimulated leukocytes through to the discovery of cryopyrin and the caspase-1 inflammasome and on to the clinical benefits of anti-IL-1beta-based therapeutics. It also discusses some of the current controversies regarding the activation of the inflammasome. The future of novel anti-inflammatory agents to combat chronic inflammation i... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338554 Wed, 03 Mar 2010 00:00:00 +0100 3338554 http://www.medworm.com/index.php?rid=3338553&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201009%26dopt%3DAbstract Authors: COVER IMAGE: The cover picture features the hallmark set of scales representing the balancing of opinions in our Viewpoint series, with the cells representing the various immune components affected by altered inflammasome activation. The schematic is taken from the article by Meng and Strober (pp. 649-653), which examines the role of Nlrp3 mutations in murine models of autoinflammatory diseases. EBV TRIGGERS MULTIPLE SCLEROSIS?: Multiple sclerosis (MS) is a demyelinating disease that affects the central nervous system (CNS). In addition to genetic factors, external factors such as the environment and pathogens are also thought to contribute to MS pathogenesis. Among these candidate factors is the Epstein-Barr virus (EBV), as suggested by large seroepidemiological studies and ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338553 Wed, 03 Mar 2010 00:00:00 +0100 3338553 http://www.medworm.com/index.php?rid=3338552&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201010%26dopt%3DAbstract Authors: PMID: 20201010 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338552 Wed, 03 Mar 2010 00:00:00 +0100 3338552 http://www.medworm.com/index.php?rid=3338551&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201011%26dopt%3DAbstract Authors: Deniz G, Chapel H, Barlan I, de Vries E, Jaraquemada D PMID: 20201011 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338551 Wed, 03 Mar 2010 00:00:00 +0100 3338551 http://www.medworm.com/index.php?rid=3338550&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201012%26dopt%3DAbstract Authors: Cassel SL, Sutterwala FS Through pattern recognition receptors the innate immune system detects disruption of the normal function of the organism and initiates responses directed at correcting these derangements. Cellular damage from microbial or non-microbial insults causes the activation of nucleotide-binding domain leucine-rich repeat containing receptors in multiprotein complexes called inflammasomes. Here we discuss the role of the NLRP3 inflammasome in the recognition of cellular damage and the initiation of sterile inflammatory responses. PMID: 20201012 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338550 Wed, 03 Mar 2010 00:00:00 +0100 3338550 http://www.medworm.com/index.php?rid=3338549&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201013%26dopt%3DAbstract Authors: Franchi L, Muñoz-Planillo R, Reimer T, Eigenbrod T, Núñez G Members of the Nod-like receptor family and the adaptor ASC assemble into multiprotein platforms, termed inflammasomes, to mediate the activation of caspase-1 and subsequent secretion of IL-1beta and IL-18. Recent studies have identified microbial and endogenous molecules as well as possible mechanisms involved in inflammasome activation. PMID: 20201013 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338549 Wed, 03 Mar 2010 00:00:00 +0100 3338549 http://www.medworm.com/index.php?rid=3338548&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201014%26dopt%3DAbstract Authors: Martinon F Inflammasomes are innate immune signaling pathways that sense pathogens and injury to direct the proteolytic maturation of inflammatory cytokines such as IL-1beta and IL-18. Among inflammasomes, the NLRP3/NALP3 inflammasome is the most studied. However, little is known on the molecular mechanisms that mediate its assembly and activation. Recent findings suggest that ROS are produced by NLRP3/NALP3 activators and are essential secondary messengers signaling NLRP3/NALP3 inflammasome activation. PMID: 20201014 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338548 Wed, 03 Mar 2010 00:00:00 +0100 3338548 http://www.medworm.com/index.php?rid=3338547&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201015%26dopt%3DAbstract Authors: Hornung V, Latz E Inflammasomes are cytosolic multi-protein complexes that form in response to infectious or injurious challenges. Inflammasomes control the activity of caspase-1, which is essential for the maturation and release of IL-1beta family cytokines. The NLRP1, IPAF and AIM2 inflammasomes recognize specific substances, while the NLRP3 inflammasome responds to many structurally and chemically diverse triggers. Here, we discuss the critical roles of priming and lysosomal damage in NLRP3 inflammasome activation. PMID: 20201015 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338547 Wed, 03 Mar 2010 00:00:00 +0100 3338547 http://www.medworm.com/index.php?rid=3338546&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201016%26dopt%3DAbstract Authors: Shaw PJ, Lamkanfi M, Kanneganti TD Recent years have witnessed a marked progress in our knowledge of NOD-like receptors (NLR), intracellular sensors with central roles in innate and adaptive immunity. A majority of the research has focused on caspase-1 inflammasomes. However, several members of the mammalian NLR family exert important roles in immunity beyond inflammasome signaling. Here we highlight the emerging roles of several of these NLR. PMID: 20201016 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338546 Wed, 03 Mar 2010 00:00:00 +0100 3338546 http://www.medworm.com/index.php?rid=3338545&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201017%26dopt%3DAbstract Authors: Kepp O, Galluzzi L, Zitvogel L, Kroemer G The term "pyroptosis" was originally introduced to describe a particular form of cell death in macrophages, which is induced by bacterial infection, is accompanied by caspase-1 activation and hence leads to the release of pyrogenic interleukins; however, it is still controversial whether pyroptosis - which can also be triggered by non-bacterial pathological stimuli - truly represents a cell death modality on its own or whether it constitutes a special case of apoptosis or necrosis. PMID: 20201017 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338545 Wed, 03 Mar 2010 00:00:00 +0100 3338545 http://www.medworm.com/index.php?rid=3338544&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201018%26dopt%3DAbstract Authors: Cook GP, Savic S, Wittmann M, McDermott MF A role for NLRP3 inflammasome in recurrent and chronic inflammation was initially described in a group of rare autoinflammatory conditions, termed cryopyrin-associated periodic syndrome. Subsequently, inflammasomes have been implicated in the pathology of many common diseases, including cancer, gout and diabetes. Despite diverse pathologies, the central role of the inflammasome in innate defences and tumour elimination suggests common therapeutic approaches to reduce inflammation where appropriate. PMID: 20201018 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338544 Wed, 03 Mar 2010 00:00:00 +0100 3338544 http://www.medworm.com/index.php?rid=3338543&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201019%26dopt%3DAbstract Authors: Harris J, Sharp FA, Lavelle EC Adjuvants are essential for enhancing and directing immunity to vaccine antigens. Most adjuvants in clinical use are particulates, but how they drive innate and adaptive immune responses is unclear. A major recent advance was the demonstration that particulate adjuvants promote activation of the NLRP3 inflammasome. The mechanisms underlying this activation have been partly resolved and the role of NLRP3 in particulate adjuvant-induced adaptive immunity is currently the subject of intense interest. PMID: 20201019 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338543 Wed, 03 Mar 2010 00:00:00 +0100 3338543 http://www.medworm.com/index.php?rid=3338542&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201020%26dopt%3DAbstract Authors: Spreafico R, Ricciardi-Castagnoli P, Mortellaro A Alum has been the only adjuvant licensed for human vaccines for decades and is still widely used, but its mechanism of action remains obscure. Recently, the NLRP3 inflammasome has been linked to the immunostimulatory properties of alum and other particulate adjuvants, although it is disputed to what degree NLRP3 is genuinely essential in vivo. Meanwhile, researchers are testing adjuvants harnessing both the infectious/non-infectious-discriminating TLR and the danger-sensing NLRP3 inflammasome pathways. Could this be the basis of a long-needed rationale in the design of adjuvants? PMID: 20201020 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338542 Wed, 03 Mar 2010 00:00:00 +0100 3338542 http://www.medworm.com/index.php?rid=3338541&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201021%26dopt%3DAbstract Authors: Rodrigue-Gervais IG, Saleh M Human genetics research has had a great impact on the genesis of the inflammasome field and the treatment of certain inflammasomopathies. The identification of mutations causing rare autoinflammatory syndromes, reproductive wastage disorders and of single nucleotide polymorphisms influencing susceptibility to complex diseases such as vitiligo, sepsis, and Crohn's disease has not only led to the characterization of novel proteins involved in NOD-like receptor-coupled inflammatory signaling pathways but also to greater insights into pathogenic mechanisms. PMID: 20201021 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338541 Wed, 03 Mar 2010 00:00:00 +0100 3338541 http://www.medworm.com/index.php?rid=3338540&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201022%26dopt%3DAbstract Authors: Meng G, Strober W Mutations in the Nlrp3 (CIAS1, cryopyrin) gene are associated with cryopyrin-associated periodic syndrome, autoinflammatory diseases characterized by excessive IL-1 production and neutrophilia in blood and tissues. Recent studies with gene-targeted mice expressing mutations homologous to those found in cryopyrin-associated periodic syndrome patients have advanced the understanding of NLRP3-associated autoinflammation. In this Viewpoint, we will discuss the mechanisms of NLRP3 inflammasome activation and its induction of Th17-cell-dominant immunologic responses. PMID: 20201022 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338540 Wed, 03 Mar 2010 00:00:00 +0100 3338540 http://www.medworm.com/index.php?rid=3338539&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201023%26dopt%3DAbstract Authors: Li J, Wang Y, Liang Y, Ni B, Wan Y, Liao Z, Chan KH, Yuen KY, Fu X, Shang X, Wang S, Yi D, Guo B, Di B, Wang M, Che X, Wu Y PMID: 20201023 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338539 Wed, 03 Mar 2010 00:00:00 +0100 3338539 http://www.medworm.com/index.php?rid=3338538&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201035%26dopt%3DAbstract In conclusion, an increase of cytoplasmic free zinc is required for IL-2-induced ERK signaling and proliferation of T cells. PMID: 20201035 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338538 Wed, 03 Mar 2010 00:00:00 +0100 3338538 http://www.medworm.com/index.php?rid=3338537&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201036%26dopt%3DAbstract Authors: Lévesque SA, Kukulski F, Enjyoji K, Robson SC, Sévigny J P2X(7) receptor is an ATP-gated ion channel within the multiprotein inflammasome complex. Until now, little is known about regulation of P2X(7) effector functions in macrophages. Here, we show that NTPDase1/CD39 is the dominant ectonucleotidase expressed by murine peritoneal macrophages and that it regulates P2X(7)-dependent responses in these cells. Macrophages isolated from NTPDase1-null mice (Entpd1(-/-)) were devoid of all ADPase and most ATPase activities when compared to wild type macrophages (Entpd1(+/+)). Entpd1(-/-) macrophages exposed to millimolar concentrations of ATP were more susceptible to cell death, released more IL-1â and IL-18 after TLR2 or TLR4 priming, and incorporated the fluorescent ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338537 Wed, 03 Mar 2010 00:00:00 +0100 3338537 http://www.medworm.com/index.php?rid=3338536&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201037%26dopt%3DAbstract Authors: Gründemann C, Schwartzkopff S, Koschella M, Schweier O, Peters C, Voehringer D, Pircher H The killer cell lectin-like receptor G1 (KLRG1) is expressed by NK and T cell subsets and recognizes members of the classical cadherin family. KLRG1 is widely used as a lymphocyte differentiation marker in both humans and mice but the physiological role of KLRG1 in vivo is still unclear. Here, we generated KLRG1-deficient mice by homologous recombination and used several infection models for their characterization. The results revealed that KLRG1-deficiency did not affect development and function of NK cells examined under various conditions. KLRG1 was also dispensable for normal CD8+ T cell differentiation and function after viral infections. Thus, KLRG1 is a marker for distinct NK ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338536 Wed, 03 Mar 2010 00:00:00 +0100 3338536 http://www.medworm.com/index.php?rid=3338535&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201038%26dopt%3DAbstract Authors: Monsiváis-Urenda A, Noyola-Cherpitel D, Hernández-Salinas A, García-Sepúlveda C, Romo N, Baranda L, López-Botet M, González-Amaro R Human cytomegalovirus (hCMV) infection is usually asymptomatic but may cause disease in immunocompromised hosts. It has been reported that hCMV infection may shape the NK cell receptor (NKR) repertoire in adult individuals, promoting a variable expansion of the CD94/NKG2C+NK cell subset. We explored the possible relationship between this viral infection and the expression pattern of different NKR including: CD94/NKG2C, CD94/NKG2A, ILT2 (CD85j), KIR2DL1/2DS1, KIR3DL1 and CD161 in peripheral blood lymphocytes from healthy children, seropositive (n=21) and seronegative (n=20) for hCMV. Consistent with previous observatio... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338535 Wed, 03 Mar 2010 00:00:00 +0100 3338535 http://www.medworm.com/index.php?rid=3338534&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201039%26dopt%3DAbstract In this study we addressed this question using CCL19-deficient mice expressing various levels of CCL21. Complete deficiency of CCL19 and CCL21 but not CCL19 alone was found to be associated with abnormal frequencies and localization of DC in naïve LN. Similarly, CCL19 was not required for DC migration from the skin, full DC maturation and efficient T-cell priming. Our findings suggest that CCL21 is the critical CCR7 ligand regulating DC homeostasis and function in vivo with CCL19 being redundant for these processes. PMID: 20201039 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338534 Wed, 03 Mar 2010 00:00:00 +0100 3338534 http://www.medworm.com/index.php?rid=3338533&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201040%26dopt%3DAbstract Authors: Crawley AM, Vranjkovic A, Young C, Angel JB Signalling via the IL-7 receptor complex (IL-7Ralpha/CD127 and IL-2Rgamma/CD132) is required for T-cell development and survival. Decreased CD127 expression has been associated with persistent viral infections (e.g. HIV, HCV) and cancer. Many IL-2Rgamma-sharing (gamma(C)) cytokines decrease CD127 expression on CD4(+) and CD8(+) T-cells in mice (IL-2, -4, -7, -15) and in humans (IL-2, -7) suggesting a common function. IL-4 is of particular interest as it is upregulated in HIV infection and in thyroid and colon cancers. The role of IL-4 in regulating CD127 expression and IL-7 activity in human thymocytes and mature CD8(+) T-cells is unknown andwas therefore investigated. IL-4 decreased CD127 expression on all thymocyte subsets tested a... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338533 Wed, 03 Mar 2010 00:00:00 +0100 3338533 http://www.medworm.com/index.php?rid=3338532&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201041%26dopt%3DAbstract Authors: Hansmann L, Schmidl C, Boeld TJ, Andreesen R, Hoffmann P, Rehli M, Edinger M PMID: 20201041 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338532 Wed, 03 Mar 2010 00:00:00 +0100 3338532 http://www.medworm.com/index.php?rid=3338531&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201042%26dopt%3DAbstract Authors: Matskevich AA, Quintin J, Ferrandon D The Drosophila Toll signalling pathway controls the systemic antifungal host response. Gram-negative binding protein 3 (GNBP3), a member of the â-Glucan recognition protein (âGRP) family, senses fungal infections and activates this pathway. A second detection system perceives the activity of proteolytic fungal virulence factors and redundantly activates Toll. GNBP3(hades) mutant flies succumb more rapidly to Candida albicans and to entomopathogenic fungal infections than wild type (WT) flies, despite normal triggering of the Toll pathway via the virulence detection system. These observations suggest that GNBP3 triggers antifungal defenses that are not dependent on activation of the Toll pathway. Here, we show that GNBP3 agglutina... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338531 Wed, 03 Mar 2010 00:00:00 +0100 3338531 http://www.medworm.com/index.php?rid=3338530&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201043%26dopt%3DAbstract Authors: Cella M, Presti R, Vermi W, Lavender K, Turnbull E, Ochsenbauer-Jambor C, Kappes JC, Ferrari G, Kessels L, Williams I, McMichael AJ, Haynes BF, Borrow P, Colonna M, , The hallmark of chronic viral infections is a progressive exhaustion of antigen specific CD8(+) T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8(+) T cells that makes them dysfunctional. Here we show that during human chronic HIV-1 infection a CD8(+) T cell positive costimulatory pathway mediated by DNAM-1 is also disrupted. Thus, DNAM-1 downregulation on CD8(+) T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection. PMID: 20201043 [PubMed - as supplied by pu... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3338530 Wed, 03 Mar 2010 00:00:00 +0100 3338530 http://www.medworm.com/index.php?rid=3331798&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20186876%26dopt%3DAbstract Authors: Wang LX, Li Y, Yang G, Pang PY, Haley D, Walker EB, Urba WJ, Hu HM Lymphodeleption prior to adoptive transfer of tumor-specific T cells greatly improves the clinical efficacy of adoptive T-cell therapy for patients with advanced melanoma, and increases the therapeutic efficacy of cancer vaccines in animal models. Lymphodepletion reduces competition between lymphocytes, and thus creates "space" for enhanced expansion and survival of tumor-specific T cells. Within the lymphodepleted host, antigen-specific T cells still need to compete with other lymphocytes that undergo lymphopenia-driven proliferation. Herein we describe the relative capacity of naïve, regulatory T cells, and NK cells to undergo lymphopenia-driven proliferation. We found that the major population that unde... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3331798 Tue, 23 Feb 2010 00:00:00 +0100 3331798 http://www.medworm.com/index.php?rid=3331797&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20186877%26dopt%3DAbstract Authors: Kondo S, Kishi H, Muraguchi A The strength of the interaction between the antigenic peptide-loaded MHC (MHC/p) and the TCR determines T-cell fate in the thymus. A high avidity interaction between the TCR and the MHC/p induces apoptosis of self-reactive T cells (negative selection), whereas a moderate avidity interaction rescues thymocytes from apoptosis and permits further differentiation to mature T cells (positive selection). Leukocyte common antigen-related molecule (LAR), a receptor-like protein tyrosine phosphatase, is expressed on immature thymocytes, but its role in thymocyte differentiation has not yet been fully elucidated. We analyzed LAR-deficient mice and demonstrated that LAR-deficiency affected the differentiation and expansion of immature thymocytes as well as p... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3331797 Tue, 23 Feb 2010 00:00:00 +0100 3331797 http://www.medworm.com/index.php?rid=3331796&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20186878%26dopt%3DAbstract In conclusion, we show that different vectors can induce completely different recognition of the same protein. PMID: 20186878 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3331796 Tue, 23 Feb 2010 00:00:00 +0100 3331796 http://www.medworm.com/index.php?rid=3331795&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20186879%26dopt%3DAbstract We report that DC from Mapk3(-/-) mice have a significantly higher membrane expression of CD86 and MHC-II and - when loaded with the myelin oligodendrocyte glycoprotein (MOG) - show a superior capacity to prime naïve T cells towards an inflammatory phenotype than Mapk3(+/+)DC. Nonetheless and as previously described, Mapk3(-/-) mice were only slightly but not significantly more susceptible to MOG-induced EAE than wildtype littermate mice. However, Mapk3(+/+) mice engrafted with Mapk3(-/-) bone marrow (KOWT) developed a severe form of EAE, in direct contrast to WTKO mice, which were even less sick than control WTWT mice. An infiltration of DC and accumulation of Th17 cells was also observed in the CNS of KOWT mice. Therefore triggering of MAPK3 in the periphery might be a therapeutic o... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3331795 Tue, 23 Feb 2010 00:00:00 +0100 3331795 http://www.medworm.com/index.php?rid=3331794&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20186880%26dopt%3DAbstract Authors: Marquardt N, Wilk E, Pokoyski C, Schmidt RE, Jacobs R Human Natural Killer (NK) cells can be subdivided into CD56(dim) and CD56(bright) NK cells, which exhibit different phenotypical and functional characteristics. As murine NK cells lack CD56 or a distinct correlate, direct comparative studies of NK cells in mice and humans are limited. Although CD27 is currently proposed as a feasible subset marker in mice, we assume that the usage of this marker alone is insufficient. We rather investigated the expression of the chemokine receptor CXCR3 for its suitability for distinguishing murine NK cell subsets with simultaneous consideration of CD27. Compared to CXCR3(-) NK cells, exerting stronger cytotoxic capability, CXCR3(+) NK cells displayed an activated phenotype with a lower exp... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3331794 Tue, 23 Feb 2010 00:00:00 +0100 3331794 http://www.medworm.com/index.php?rid=3331799&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20186746%26dopt%3DAbstract Authors: Sacks SH The influence of complement on B-cell responses has been known for many years, but the notion that T-cell recognition, expansion and differentiation are complement dependent has only recently gained impetus. DC, and to a lesser extent T cells, produce a range of complement components necessary for complement activation, and these cells also express receptors that detect complement-activation products such as C3a and C5a (anaphylatoxins). In the absence of C3a-receptor (C3aR) signalling, DC lose their capacity to induce potent Th1 responses against alloantigen and also favour the emergence of Treg. A study in this issue of the European Journal of Immunology not only spotlights the importance of C5aR signalling in DC interaction with T cells, but also shows how cooperat... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3331799 Mon, 22 Feb 2010 00:00:00 +0100 3331799 http://www.medworm.com/index.php?rid=3288295&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20162549%26dopt%3DAbstract Authors: Hamatake M, Komano J, Urano E, Maeda F, Nagatsuka Y, Takekoshi M HIV replication is restricted by some anti-CD4 mouse mAb in vitro and in vivo. However, a human monoclonal anti-CD4 Ab has not been isolated. We screened EBV-transformed peripheral B cells from 12 adult donors for CD4-reactive Ab production followed by functional reconstitution of Fab genes. Three independent IgM Fab clones reactive specifically to CD4 were isolated from a healthy HIV-seronegative adult ( approximately 0.0013% of the peripheral B cells). The germ line combinations for the VH and VL genes were VH3-33/L6, VH3-33/L12, and VH4-4/L12, respectively, accompanied by somatic hypermutations. Genetic analysis revealed a preference for V gene usage to develop CD4-reactive Ab. Notably, one of the CD4-reactive... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3288295 Tue, 16 Feb 2010 00:00:00 +0100 3288295 http://www.medworm.com/index.php?rid=3288294&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20162550%26dopt%3DAbstract Authors: Emoto M, Emoto Y, Yoshizawa I, Kita E, Shimizu T, Hurwitz R, Brinkmann V, Kaufmann SH alpha-galactosylceramide (alpha-GalCer) activates invariant (i)NKT cells, which in turn stimulate immunocompetent cells. Although activation of iNKT cells appears critical for regulation of immune responses, it remains elusive whether protection against intracellular bacteria can be induced by alpha-GalCer. Here we show that alpha-GalCer treatment ameliorates murine listeriosis, and inhibits inflammation following Listeria monocytogenes infection. Liver infiltration of Gr-1(+) cells and gamma/delta T cells was accelerated by alpha-GalCer treatment. Gr-1(+) cells and gamma/delta T cell depletion exacerbated listeriosis in alpha-GalCer-treated mice, and this effect was more pronounced after dep... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3288294 Tue, 16 Feb 2010 00:00:00 +0100 3288294 http://www.medworm.com/index.php?rid=3288293&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20162551%26dopt%3DAbstract Authors: Chen Y, Wermeling F, Sundqvist J, Jonsson AB, Tryggvason K, Pikkarainen T, Karlsson MC Recognition of microbial components by TLRs, key sensors of infection, leads to induction of inflammatory responses. We found that, in vivo, TLR4 engagement by LPS induces up-regulation of class A scavenger receptors (SRs) MARCO and SR-A, which occurs, at least in case of MARCO, via both MyD88-dependent and -independent pathways.When challenging mice with a low dose of LPS followed by a high dose, class A SR-deficient mice showed a higher survival rate than WT mice. This was paired with increased production of IL-10 and anti-LPS Abs, as well as increased activation status of marginal zone (MZ) B-cells. However, the receptors were not crucial for survival when challenging mice i.p. with Neiss... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3288293 Tue, 16 Feb 2010 00:00:00 +0100 3288293 http://www.medworm.com/index.php?rid=3288292&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20162552%26dopt%3DAbstract This study indicates that H2-M3-restricted T cells promote immune responses by CD4(+) T cells by inducing DC maturation and suggests novel mechanisms for vaccine development. PMID: 20162552 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3288292 Tue, 16 Feb 2010 00:00:00 +0100 3288292 http://www.medworm.com/index.php?rid=3288291&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20162553%26dopt%3DAbstract This study provides a stepping stone towards further investigation of autophagy in neutrophil-driven inflammatory disorders. PMID: 20162553 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3288291 Tue, 16 Feb 2010 00:00:00 +0100 3288291 http://www.medworm.com/index.php?rid=3288290&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20162554%26dopt%3DAbstract Authors: Gabryšová L, Wraith DC Intranasal (i.n.) administration of peptides induces peripheral tolerance in Tg4 myelin basic protein (MBP)-specific TCR-transgenic mice. This is characterized by the generation of anergic, IL-10-secreting CD4(+) T (IL-10 Treg) cells with regulatory function. MBP Ac1-9 peptide analogs, displaying a hierarchy of affinities for H-2 A(u) (Ac1-9[4K]<<[4A]<[4Y]), were used to investigate the mechanisms of tolerance induction, focusing on IL-10 Treg cell generation. Repeated i.n. administration of the highest affinity peptide, Ac1-9[4Y], provided complete protection against EAE, while i.n. Ac1-9[4A] and Ac1-9[4K] treatment resulted in only partial protection. Ac1-9[4Y] was also the most potent stimulus for IL-10 Treg cell generation. Althou... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3288290 Tue, 16 Feb 2010 00:00:00 +0100 3288290 http://www.medworm.com/index.php?rid=3288289&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20162555%26dopt%3DAbstract Authors: Hori S The transcription factor Foxp3 controls the differentiation and function of regulatory T cells (Treg), but the molecular mechanisms that regulate Foxp3 transcription remain elusive. In particular, signals and factors that open and remodel the Foxp3 locus and imprint developing Treg with a stable Foxp3 phenotype are largely unknown. Two reports in this issue of the European Journal of Immunology, together with recent reports published elsewhere, demonstrate that a member of the NF-kappaB family transcription factors, c-Rel, is required for thymic differentiation of Foxp3(+) Treg. Moreover, c-Rel is shown to regulate Foxp3 transcription directly by binding to cis-regulatory elements at the Foxp3 locus upon TCR/CD28 stimulation, including the promoter and the newly identif... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3288289 Tue, 16 Feb 2010 00:00:00 +0100 3288289 http://www.medworm.com/index.php?rid=3263690&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200940102 Persistent viral infections are, by definition, associated with ineffective antiviral immunity, in particular those infections caused by viruses that are highly productive and replicative (including HIV, HBV and HCV). The reasons for ineffective antiviral immunity in these types of infections are complex and manifold, and only recently a more comprehensive picture of the parameters responsible for attenuation of immune function is emerging. One reason for poor viral control in these types of infections is the functional deterioration of antiviral T-cell responses and understanding the underlying mechanisms is of key importance. This review summarizes our current knowledge of cell-intrinsic and cell-extrinsic parameters that contribute to T-cell exhaustion during chronic viral infections an... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3263690 Fri, 12 Feb 2010 00:00:00 +0100 3263690 http://www.medworm.com/index.php?rid=3270182&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20148420%26dopt%3DAbstract Authors: Lindberg RL, Hoffmann F, Mehling M, Kuhle J, Kappos L MicroRNA (miRNA) are a class of post-transcriptional regulators of gene expression targeting mRNA for translational repression and/or degradation. We analyzed the expression of 365 miRNA in lymphocytes in relapsing-remitting MS patients, and show the first evidence for distinct miRNA expression profiles in CD4(+), CD8(+) and B cells in MS when compared with those in healthy volunteers. MiR-17-5p, which is involved in autoimmunity, was up-regulated in CD4(+) cells from MS patients. This was correlated with alterations in the expression of potential target genes of miR-17-5p, i.e. phosphatase and tensin homology and phosphatidyl-inositol-3-kinase regulatory subunit 1, which were down-regulated upon stimulation of CD4(+) cells... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3270182 Wed, 10 Feb 2010 00:00:00 +0100 3270182 http://www.medworm.com/index.php?rid=3270181&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20148421%26dopt%3DAbstract We examined the impact of antigen presentation and T cell stimulation on allergic airway hyperresponsiveness and inflammation using transgenic and gene deficient mice. Both airway inflammation and eosinophilia in bronchoalveolar lavage fluid were markedly reduced in sensitized and challenged FcRgamma-deficient mice. Lung DC of wildtype, but not FcRgamma-deficient mice, induced increased antigen-specific CD4(+) T cell proliferation when pulsed with anti-ovalbumin IgG immune complexes (OVA-IC). Intranasal application of OVA-IC resulted in enhanced airway inflammation, eosinophilia and Th2 cytokine release, mediated through enhanced antigen-specific T cell proliferation in vivo. Finally, antigen-specific IgG in the serum of sensitized mice lead to a significant increase of antigen-specific CD... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3270181 Wed, 10 Feb 2010 00:00:00 +0100 3270181 http://www.medworm.com/index.php?rid=3270180&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20148422%26dopt%3DAbstract Authors: Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA Allergy is a Th2-mediated disease that involves the formation of specific IgE antibodies against innocuous environmental substances. The prevalence of allergic diseases has dramatically increased over the past decades, affecting up to 30% of the population in industrialized countries. The understanding of mechanisms underlying allergic diseases as well as those operating in non-allergic healthy responses and allergen-specific immunotherapy has experienced exciting advances over the past 15 years. Studies in healthy non-atopic individuals and several clinical trials of allergen-specific immunotherapy have demonstrated that the induction of a tolerant state in peripheral T cells represent a key step in healthy immune res... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3270180 Wed, 10 Feb 2010 00:00:00 +0100 3270180 http://www.medworm.com/index.php?rid=3270179&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20148423%26dopt%3DAbstract Authors: Kim JI, Sonawane SB, Lee MK, Lee SH, Duff PE, Moore DJ, O'Connor MR, Lian MM, Deng S, Choi Y, Yeh H, Caton AJ, Markmann JF Involvement of regulatory T cells (Treg) in transplant tolerance has been demonstrated in multiple models. During the active process of graft rejection, these regulatory cells are themselves regulated and inactivated, a process termed counter-regulation. We hypothesize that ligation of the costimulatory molecule glucocorticoid-induced TNF receptor-related protein (GITR) on Treg inhibits their ability to promote graft survival, and by blocking GITR ligation graft survival can be prolonged. To this aim we have designed a soluble GITR fusion protein (GITR-Fc), which binds GITRL and inhibits activation of GITR. Here we show that GITR-Fc prolonged mouse skin gr... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3270179 Wed, 10 Feb 2010 00:00:00 +0100 3270179 http://www.medworm.com/index.php?rid=3263698&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200940032 MicroRNA (miRNA) are a class of post-transcriptional regulators of gene expression targeting mRNA for translational repression and/or degradation. We analyzed the expression of 365 miRNA in lymphocytes in relapsing-remitting MS patients, and show the first evidence for distinct miRNA expression profiles in CD4+, CD8+ and B cells in MS when compared with those in healthy volunteers. MiR-17-5p, which is involved in autoimmunity, was up-regulated in CD4+ cells from MS patients. This was correlated with alterations in the expression of potential target genes of miR-17-5p, i.e. phosphatase and tensin homology and phosphatidyl-inositol-3-kinase regulatory subunit 1, which were down-regulated upon stimulation of CD4+ cells with anti-CD3/CD28 in vitro. Functional experiments with a synthetic inhib... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3263698 Wed, 10 Feb 2010 00:00:00 +0100 3263698 http://www.medworm.com/index.php?rid=3255548&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20140902%26dopt%3DAbstract In conclusion, LL-37 modulates the response of neutrophils to bacterial activation. Cathelicidin controls the release of inflammatory mediators while increasing antimicrobial activity of neutrophils. PMID: 20140902 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3255548 Fri, 05 Feb 2010 00:00:00 +0100 3255548 http://www.medworm.com/index.php?rid=3255547&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20140903%26dopt%3DAbstract Authors: De Colvenaer V, Taveirne S, Hamann J, de Bruin A, De Smedt M, Taghon T, Vandekerckhove B, Plum J, Van Lier R, Leclercq G Natural killer (NK) cells are important mediators of the early defense. In mice, immature and mature NK cells constitutively express the TNF receptor family member CD27. However, mature NK cells eventually lose CD27 expression and become resting NK cells. Interaction of CD27 with its ligand, CD70, enhances proliferation and effector functions of NK cells. We used mice that constitutively express CD70 on B cells (CD70-Tg) to study the in vivo effects of continuous triggering of CD27 on NK cells. Continuous CD70-CD27 interaction resulted in strongly down-modulated CD27 expression on NK cells and gradually reduced absolute NK cell numbers. This reduction was mo... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3255547 Fri, 05 Feb 2010 00:00:00 +0100 3255547 http://www.medworm.com/index.php?rid=3255546&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20140904%26dopt%3DAbstract Authors: Xu R, Wang R, Han G, Wang J, Chen G, Wang L, Li X, Guo R, Shen B, Li Y Complement 5a (C5a) and Interleukin-17 (IL-17) are two important inflammatory mediators in sepsis. Here we studied the mechanisms underlying regulation of IL-17 by anaphylatoxin C5a. We found that C5a blockade increased survival rate in cecal ligation and puncture (CLP)-induced sepsis and decreased IL-17 expression in vivo. IL-17 was secreted mainly by gammadelta T cells in this model. Importantly, our data suggest that C5a participates in the regulation of gammadelta T cells to secrete IL-17. Dendritic cells (DCs) were found to act as a "bridge" between C5a and gammadelta T cells in a mechanism involving IL-6 and transforming growth factor beta (TGF-beta). These results imply that C5a affects the crosstalk... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3255546 Fri, 05 Feb 2010 00:00:00 +0100 3255546 http://www.medworm.com/index.php?rid=3364284&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200940022 In this study, we report that human peripheral blood (PB) FOXP3+ cells present in CD25high, CD25low and even CD25- subsets of CD4+ cells expressed high levels of TNFR2. Consequently, TNFR2-expressing CD4+CD25+ Treg included all of the FOXP3+ cells present in the CD4+CD25high subset as well as a substantial proportion of the FOXP3+ cells present in the CD4+CD25low subset. Flow cytometric analysis of PB identified five-fold more Treg, determined by FOXP3 expression, in the CD4+CD25+TNFR2+ subset than in the CD4+CD25high subset. In addition, similar levels of FOXP3+ cells were identified in both the CD4+CD25+TNFR2+ and CD4+CD25+CD127low/- subsets. Furthermore, the CD4+CD25+TNFR2+ subset expressed high levels of CTLA-4, CD45RO, CCR4 and low levels of CD45RA and CD127, a phenotype characteristi... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3364284 Mon, 01 Feb 2010 00:00:00 +0100 3364284 http://www.medworm.com/index.php?rid=3332320&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939664 Successful resolution of inflammation requires inflammatory cells such as neutrophils to undergo apoptosis prior to non-inflammatory phagocytosis by professional phagocytes. Recently, cyclin-dependent kinase (CDK) inhibitors (e.g. R-roscovitine) have been shown to induce neutrophil apoptosis and enhance the resolution of inflammation. Interestingly, NF-[kappa]B and MAPK pathways and key endogenous survival proteins (typified by Mcl-1) are involved in the regulation of neutrophil apoptosis and, in cancer-cell lines, have been implicated as possible targets of CDK inhibitors. Here, we demonstrate that R-roscovitine over-rides TNF-[alpha] and LPS-induced survival (determined by morphological examination and binding of fluorescently labelled annexin-V) of isolated peripheral blood neutrophils.... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3332320 Mon, 01 Feb 2010 00:00:00 +0100 3332320 http://www.medworm.com/index.php?rid=3295322&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939485 To develop cytolytic effector functions, CD8+ T lymphocytes need to recognize specific Ag/MHC class I complexes in the context of costimuli on Ag-presenting DC. Thereafter they differentiate into effector and memory CTL able to confer protection against pathogen infection. Using transgenic mice with DC-selective MHC class I expression and DC-specific versus ubiquitous vaccination regimen, we found that DC are sufficient to prime CTL responses. However, Ag recognition on parenchymal non-professional APC negatively affected CD8+ T-cell responses in mice by inducing expression of the pro-apoptotic bcl2-family member bim in CTL. This unexpected induction of apoptosis in the early phase of effector CTL accumulation lead to suboptimal clonal burst size and diminished long-term memory. Thus, our ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3295322 Mon, 01 Feb 2010 00:00:00 +0100 3295322 http://www.medworm.com/index.php?rid=3240003&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127673%26dopt%3DAbstract Authors: Scheeren FA, van Lent AU, Nagasawa M, Weijer K, Spits H, Legrand N, Blom B Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL-7Ralpha chain and a unique TSLP-Receptor (TSLPR) chain. The role of TSLP in human B-cell development has not been elucidated. We show that TSLPR transcripts are expressed most prominently in CD34(+) cells from fetal liver and bone marrow. In general, cell surface expression of TSLPR was low, except on a subset of multilineage commited progenitor cells (MLCP). TSLP induced the tyrosine-phosphorylation of STAT5 and the proliferation of MLCP, pro-B cells and pre-B cells. Compared to IL-7, the levels of proliferation after stimulation of the B-cell progenitors with TSLP were lower. Expression of the BCR on the cell surface of fetal cells wa... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3240003 Mon, 01 Feb 2010 00:00:00 +0100 3240003 http://www.medworm.com/index.php?rid=3240002&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127674%26dopt%3DAbstract Authors: Gruber A, Cannarile MA, Cheminay C, Ried C, Marconi P, Häcker G, Brocker T To develop cytolytic effector functions, CD8+ T lymphocytes need to recognize specific antigen/MHC class I complexes in the context of costimuli on antigen-presenting dendritic cells (DC). Thereafter they differentiate into effector and memory cytotoxic T lymphocytes (CTL) able to confer protection against pathogen infection. Using transgenic mice with DC-selective MHC class I expression and DC-specific versus ubiquitous vaccination regimen, we found that DC are sufficient to prime CTL responses. However, antigen recognition on parenchymal non-professional antigen-presenting cells (APC) negatively affected CD8(+) T cell responses in mice by inducing expression of the pro-apoptotic bcl2-family membe... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3240002 Mon, 01 Feb 2010 00:00:00 +0100 3240002 http://www.medworm.com/index.php?rid=3240001&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127675%26dopt%3DAbstract Authors: Ohkusu-Tsukada K, Toda M, Udono H, Kawakami Y, Takahashi K Cancer-induced immunotolerance mediated by inducible T regulatory cells (iTreg) is a major obstacle to cancer immunotherapy. In a basic study of immunotolerance, injection of an endogenous superantigen, i.e., the minor lymphocyte stimulatory (Mls)-1(a), into specific TCR Vbeta8.1-transgenic mice (Vbeta8.1-Tg) enabled generation of anergic CD25(-) iTreg whose immunosuppressive function was maintained by IL-10 production via p38-MAPK activation. Interestingly, although p38-chemical inhibitor (p38-inhibitor) is capable of breaking CD25(-) iTreg-induced immunotolerance, the p38-inhibitor had hardly any immunotolerance breaking effect when CD25(+) Treg were present, suggesting that depletion of CD25(+) Treg is necessary for... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3240001 Mon, 01 Feb 2010 00:00:00 +0100 3240001 http://www.medworm.com/index.php?rid=3240000&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127676%26dopt%3DAbstract Authors: Leitch AE, Riley NA, Sheldrake T, Festa M, Fox S, Duffin R, Haslett C, Rossi AG Successful resolution of inflammation requires inflammatory cells such as neutrophils to undergo apoptosis prior to non-inflammatory phagocytosis by professional phagocytes. Recently, cyclin-dependent kinase (CDK) inhibitors (e.g. R-roscovitine) have been shown to induce neutrophil apoptosis and enhance the resolution of inflammation. Interestingly, NF-kappaB and MAPK pathways and key endogenous survival proteins (typified by Mcl-1) are involved in the regulation of neutrophil apoptosis and, in cancer-cell lines, have been implicated as possible targets of CDK inhibitors. Here we demonstrate that R-roscovitine over-rides TNF-alpha and LPS-induced survival (determined by morphological examination an... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3240000 Mon, 01 Feb 2010 00:00:00 +0100 3240000 http://www.medworm.com/index.php?rid=3239999&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127677%26dopt%3DAbstract Authors: Carson WF, Cavassani KA, Ito T, Schaller M, Ishii M, Dou Y, Kunkel SL Immunosuppression following severe sepsis remains a significant human health concern, as long-term morbidity and mortality rates of patients who have recovered from life-threatening septic shock remain poor. Mouse models of severe sepsis indicate this immunosuppression may be partly due to alterations in myeloid cell function; however, the effect of severe sepsis on subsequent CD4+ T cell responses remains unclear. In the present study, CD4+ T cells from mice subjected to an experimental model of severe sepsis (cecal ligation and puncture, CLP) were analyzed in vitro. CD4+ CD62L+ T cells from CLP mice exhibited reduced proliferative capacity and altered gene expression. Additionally, CD4+ CD62L+ T cells from... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3239999 Mon, 01 Feb 2010 00:00:00 +0100 3239999 http://www.medworm.com/index.php?rid=3239998&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127678%26dopt%3DAbstract Authors: Lin BS, Tsai PY, Hsieh WY, Tsao HW, Liu MW, Grenningloh R, Wang LF, Ho IC, Miaw SC The function of transcription factors can be critically regulated by SUMOylation. c-Maf, the cellular counterpart of v-maf oncogene, is a potent transactivator of the IL-4 gene in type 2 T helper (Th2) cells. We found in a yeast two-hybrid screen that c-Maf can interact with Ubc9 and PIAS1, two key enzymes of the SUMOylation pathway. In the present study, we report that c-Maf co-localizes with these two SUMO ligases in the nucleus and that c-Maf can be SUMOylated in vitro and also in primary Th2 cells. We also demonstrated that lysine-33 is the dominant, if not the only, SUMO acceptor site of c-Maf. SUMOylation of c-Maf attenuates its transcriptional activity. Reciprocally, a SUMOylation resista... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3239998 Mon, 01 Feb 2010 00:00:00 +0100 3239998 http://www.medworm.com/index.php?rid=3239997&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127679%26dopt%3DAbstract In this study, we identified CD44 on Jurkat T cells as a candidate ligand of LSECtin, and confirmed the specific interaction between LSECtin and CD44. Moreover, we showed that LSECtin selectively bound CD44S, CD44V4 and CD44V8-10 by screening a series of typical CD44 isoforms. By deletion of the CRD region and mutation of crucial amino acids involved in carbohydrate-recognition of LSECtin and by inhibition of the N-linked glycosylation of CD44, we further demonstrated that the interaction between CD44 and LSECtin is dependent on protein-glycan recognition. Our findings indicate that CD44 is the first identified endogenous ligand of LSECtin, and similarly, thatLSECtin is a novel ligand of CD44. These findings provide important new perspectives on the biology of both LSECtin and CD44 in the ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3239997 Mon, 01 Feb 2010 00:00:00 +0100 3239997 http://www.medworm.com/index.php?rid=3239996&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127680%26dopt%3DAbstract Authors: Chen X, Subleski JJ, Hamano R, Howard OM, Wiltrout RH, Oppenheim JJ Previously we found that co-expression of CD25 and TNFR2 identified the most suppressive subset of mouse regulatory T cells (Tregs). Here, we report that human peripheral blood (PB) FoxP3(+) cells present in CD25(high), CD25(low) and even CD25(-) subsets of CD4 cells expressed high levels of TNFR2. Consequently, TNFR2-expressing CD4(+)CD25 (+) Tregs included all of FoxP3(+) cells present in CD4(+)CD25(high) subset as well as a substantial proportion of FoxP3(+) cells present in CD4(+)CD25(low) subset. CD4(+)CD25(+)TNFR2(+) cells identified 5-fold greater number of PB CD4 lymphocytes as Tregs than identified by CD4(+)CD25(high) cells, and expressed comparable levels of FoxP3(+) cells as reported CD4(+)CD25(+)CD... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3239996 Mon, 01 Feb 2010 00:00:00 +0100 3239996 http://www.medworm.com/index.php?rid=3239995&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20127681%26dopt%3DAbstract Authors: Oshiumi H, Sakai K, Matsumoto M, Seya T Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLR) are members of the DEAD box helicases, and recognize viral RNA in the cytoplasm, leading to IFN-beta induction through the adaptor IPS-1 (Cardif, MAVS or VISA). Since uninfected cells usually harbor a trace of RIG-I, other RNA-binding proteins may participate in assembling viral RNA into the IPS-1 pathway in the initial step of infection. We searched for proteins coupling with human IPS-1 by yeast two-hybrid and identified another DEAD box helicase, DDX3. DDX3 can bind viral RNA to join it in the IPS-1 complex. Unlike RIG-I, DDX3 was constitutively expressed in cells, and some fraction of DDX3 is colocalized with IPS-1 around mitochondria. The 622-662 a.a DDX3 C-terminal region ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3239995 Mon, 01 Feb 2010 00:00:00 +0100 3239995 http://www.medworm.com/index.php?rid=3225343&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939897 We describe the expression of all four known adenosine receptors A1R, A2aR, A2bR and A3R on mouse iNKT cells. We show that IL-4 production in primary mouse iNKT cells and a human iNKT line is efficiently inhibited by A2aR blockade with an inverse relation to IL-4. These data are supported by A2aR-deficient mice, which exhibit largely decreased levels of IL-4, IL-10 and TGF-[beta] concomitantly with an increase of IFN-[gamma] upon [alpha]-galactosylceramide administration in vivo. While A2aR inhibits other lymphocyte populations, A2aR is required for the secretion of IL-4 and IL-10 by iNKT cells. These data suggest adenosine:A2aR-mediated mechanisms can control the cytokine secretion pattern of iNKT cells. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225343 Mon, 01 Feb 2010 00:00:00 +0100 3225343 http://www.medworm.com/index.php?rid=3319095&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939703 Human monocytes respond to a variety of stimuli with a complex spectrum of activities ranging from acute defense mechanisms to cell differentiation or cytokine release. However, the individual intracellular signaling pathways related to these functions are not well understood. CXC chemokine ligand 4 (CXCL4) represents a broad activator of monocytes, which induces acute as well as delayed activities in these cells including cell differentiation, survival, or the release of ROS, and cytokines. Here, we report for the first time that CXCL4-treated monocytes significantly upregulate sphingosine kinase 1 (SphK1) mRNA and that CXCL4 induces SphK1 enzyme activity as well as its translocation to the cell membrane. Furthermore, we could show that pharmacological inhibition of SphK results in revers... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3319095 Tue, 26 Jan 2010 00:00:00 +0100 3319095 http://www.medworm.com/index.php?rid=3295323&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200940041 We present evidence here that hBD3 lacks pro-inflammatory activity in human and mouse primary M[phis]. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF-[alpha] and IL-6 accumulation implying an anti-inflammatory function. hBD3 also inhibits CD40/IFN-[gamma] stimulation of M[phis] and in vivo, hBD3 significantly reduces the LPS-induced TNF-[alpha] level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3295323 Tue, 26 Jan 2010 00:00:00 +0100 3295323 http://www.medworm.com/index.php?rid=3221205&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104487%26dopt%3DAbstract We examined the frequency, function and phenotype of HLA-C restricted CTL in 10 antiretroviral therapy-naïve Caucasian and African individuals with chronic HIV-1 infection (for at least 8 years and CD4 counts range 50-350) who carried the HLA-Cw04 allele. HLA-Cw04 restricted CTL that recognize a conserved epitope within HIV-1 envelope (aa 375-383 SF9) were analyzed using IFN-gamma ELISPOT assays and phenotypic analysis by flow cytometry.HLA-C restricted CTL play an important role in the HIV specific response, and can account for as much as 54% of the total response. HLA-C restricted CTL are functionally and phenotypically identical to HLA-A and -B restricted CTL. HLA-C restricted CTL in chronic HIV infection are memory cells of an intermediate phenotype, characterized by high CD27 and... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221205 Tue, 26 Jan 2010 00:00:00 +0100 3221205 http://www.medworm.com/index.php?rid=3221204&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104488%26dopt%3DAbstract Authors: Kasper B, Winoto-Morbach S, Mittelstädt J, Brandt E, Schütze S, Petersen F Human monocytes respond to a variety of stimuli with a complex spectrum of activities ranging from acute defense mechanisms to cell differentiation or cytokine release. However, the individual intracellular signaling pathways related to these functions are not well understood. CXC chemokine ligand 4 (CXCL4) represents a broad activator of monocytes, which induces acute as well as delayed activities in these cells including cell differentiation, survival, or the release of reactive oxygen species, and cytokines. Here, we report for the first time that CXCL4-treated monocytes significantly upregulate sphingosine kinase 1 (SphK1) mRNA and that CXCL4 induces SphK1 enzyme activity as well as its tr... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221204 Tue, 26 Jan 2010 00:00:00 +0100 3221204 http://www.medworm.com/index.php?rid=3221203&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104489%26dopt%3DAbstract Authors: Zuckerman NS, Howard WA, Bismuth J, Gibson K, Edelman H, Berrih-Aknin S, Dunn-Walters D, Mehr R Young patients with Myasthenia Gravis (MG) frequently have ectopic GCs in their thymus. We investigated these ectopic GCs by microdissection of GC B cells and analysis of their Ig gene characteristics, in comparison to normal GCs. CDR3 length distribution, a measure of clonal variability, and Ig gene family usage, were similar in MG and normal tonsil samples. Lineage tree analysis demonstrated similar diversification and mutations per cell compared to normal control trees. Mutations were observed in the framework regions, responsible for the structural integrity of the BCR; however, these mutations were mostly conservative or neutral, confirming that a functional BCR is conserved in... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221203 Tue, 26 Jan 2010 00:00:00 +0100 3221203 http://www.medworm.com/index.php?rid=3221202&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104490%26dopt%3DAbstract Authors: Di Genova G, Savelyeva N, Suchacki A, Thirdborough SM, Stevenson FK Antigen-specific CD4(+) T cells are central to natural and vaccine-induced immunity. However an ongoing antigen-specific T-cell response can influence surrounding T cells with unrelated antigen specificities. We previously observed this bystander effect in healthy human subjects following recall vaccination with tetanus toxoid (TT). Since this interplay could be important for maintenance of memory, we have moved to a mouse model for further analysis. We investigated if boosting memory CD4(+) T cells against TT in vivo would influence injected CD4(+) TCR transgenic T cells (OT-II) specific for an unrelated ovalbumin (OVA) peptide (OVAp). We found that, if OT-II cells were pre-activated with OVAp in vitro,they s... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221202 Tue, 26 Jan 2010 00:00:00 +0100 3221202 http://www.medworm.com/index.php?rid=3221201&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104491%26dopt%3DAbstract We present evidence here that hBD3 lacks pro-inflammatory activity in human and mouse primary macrophages. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF-alpha and IL-6 accumulation implying an anti-inflammatory function. hBD3 also inhibits CD40/Interferon-gamma stimulation of macrophages and in vivo, hBD3 significantly reduces the LPS-induced TNF-alpha level in serum. Recent work has revealed hBD3 binds melanocortin receptors (MCR) but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation. PMID: 20104491 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221201 Tue, 26 Jan 2010 00:00:00 +0100 3221201 http://www.medworm.com/index.php?rid=3221200&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104565%26dopt%3DAbstract Authors: PMID: 20104565 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221200 Tue, 26 Jan 2010 00:00:00 +0100 3221200 http://www.medworm.com/index.php?rid=3221199&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104566%26dopt%3DAbstract This study identifies a complex interplay between the immune system and the host factors, such as hormones, and demonstrates that effective immunity can be profoundly influenced under such conditions. PROTECTIVE IMMUNITY IN TUBERCULOSIS - NOT WITHOUT IL-18: pp. 396-405On the 25(th) anniversary of gammadelta T cells' accidental discovery, gammadelta T cells remain poorly understood; however, the potent anti-tumor and pro-inflammatory functions of gammadelta T cells are well documented. In this issue, to further explore the interaction of gammadelta T cells with other components of the immune system, Gonçalves-Sousa et al. show that mouse Treg efficiently suppress gammadelta T cell responses both in vitro and in vivo. Treg use cell-to-cell contact to "anergize" gammadelta T cells, thus ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221199 Tue, 26 Jan 2010 00:00:00 +0100 3221199 http://www.medworm.com/index.php?rid=3221198&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104567%26dopt%3DAbstract Authors: PMID: 20104567 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221198 Tue, 26 Jan 2010 00:00:00 +0100 3221198 http://www.medworm.com/index.php?rid=3221197&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104568%26dopt%3DAbstract Authors: PMID: 20104568 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221197 Tue, 26 Jan 2010 00:00:00 +0100 3221197 http://www.medworm.com/index.php?rid=3221196&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104569%26dopt%3DAbstract Authors: Munn DH Foxp3 is a transcription factor closely associated with the Treg lineage in humans and mice. In the immune system, Foxp3 appears highly specific for Treg, and is not known to be expressed by other immune cell types. In this issue of the European Journal of Immunology, an article reports that human DC transfected with ectopic Foxp3 unexpectedly acquire an immunosuppressive phenotype. Foxp3-transfected DC suppressed proliferation of naive T cells, and biased the differentiation of CD4(+) cells into Treg-like cells that themselves expressed Foxp3. The molecular mechanism of these effects required functional activity of the immunoregulatory enzyme IDO. Thus, a transcription factor not native to DC nevertheless conferred elements of a regulatory phenotype following ectopic ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221196 Tue, 26 Jan 2010 00:00:00 +0100 3221196 http://www.medworm.com/index.php?rid=3221195&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20104570%26dopt%3DAbstract Authors: Nakhaei-Nejad M, Zhang QX, Murray AG PMID: 20104570 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3221195 Tue, 26 Jan 2010 00:00:00 +0100 3221195 http://www.medworm.com/index.php?rid=3332319&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939778 Chemokines are important mediators of the immune response to pathogens, but can also promote chronic inflammatory states. Chemokine receptor 6 (CCR6) is found on immature DC and effector/memory T cells, and binds a single ligand, CCL20, with high affinity. Here, we investigated the role of CCL20 and CCR6 in a pulmonary viral infection caused by RSV, a ubiquitous virus that can cause severe pulmonary complications. Neutralization of CCL20 during RSV infection significantly reduced lung pathology and favored a Th1 effector response. CCR6-deficient animals recapitulated this phenotype, and additionally showed enhanced viral clearance when compared with WT mice. No differences were observed in migration of T cells to the lungs of CCR6-/- animals; however, a significant reduction was observed i... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3332319 Mon, 25 Jan 2010 00:00:00 +0100 3332319 http://www.medworm.com/index.php?rid=3319096&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939848 CD19 is a B-cell transmembrane molecule that is critical for B-cell activation. CD19 serves as a scaffold protein for key signal transduction molecules including Lyn, PI3K, and Vav, by providing docking sites for these molecules via phosphorylation of CD19-Y513, CD19-Y482, and CD19-Y391. We investigated the process of CD19 tyrosine phophorylation during B-cell activation using Ab specific for each of these phosphorylated tyrosines. BCR engagement induced differential tyrosine phosphorylation, as CD19-Y513 phophorylation occurred first, and CD19-Y482 phosphorylation was delayed and transient. Different BCR isotypes exhibited distinct patterns of CD19 phosphorylation: IgG-BCR ligation resulted in faster phosphorylation of CD19-Y513 and more intense phosphorylation of CD19-Y391 than IgM-BCR l... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3319096 Mon, 25 Jan 2010 00:00:00 +0100 3319096 http://www.medworm.com/index.php?rid=3319094&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939525 When developing malaria vaccines, the most crucial step is to elucidate the mechanisms involved in protective immunity against the parasites. We found that CD8+ T cells contribute to protective immunity against infection with blood-stage parasites of Plasmodium yoelii. Infection of C57BL/6 mice with P. yoelii 17XL was lethal, while all mice infected with a low-virulence strain of the parasite 17XNL acquired complete resistance against re-infection with P. yoelii 17XL. However, the host mice transferred with CD8+ T cells from mice primed only with P. yoelii 17XNL failed to acquire protective immunity. On the other hand, the irradiated host mice were completely resistant to P. yoelii 17XL infection, showing no grade of parasitemia when adoptively transferred with CD8+ T cells from immune mic... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3319094 Mon, 25 Jan 2010 00:00:00 +0100 3319094 http://www.medworm.com/index.php?rid=3295324&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939651 Simultaneous stimulation with antigen and adenosine in mast cells induces a synergistic degranulation response at a low antigen dose that is insufficient to cause secretion by itself. This kind of stimulation is thought to be relevant to the immediate asthmatic response upon bronchial challenge with low-dose allergen. In this context, Fc[epsiv]RI- and adenosine receptor-mediated signalings cooperate to increase degranulation in mast cells. In the present study, we prepared mast cells that have mutations (Y219F/Y225F/Y229F) in three tyrosine residues of the Fc[epsiv]RI [beta]-chain (FcR[beta])-ITAM in order to elucidate the molecular mechanisms of degranulation response synergistically elicited by costimulation with low-dose antigen and adenosine. Introduction of mutations in the FcR[beta]-... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3295324 Mon, 25 Jan 2010 00:00:00 +0100 3295324 http://www.medworm.com/index.php?rid=3295321&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939738 In this study, antigenic peptides from tetanus toxin and influenza hemagglutinin complexed to human stress-inducible Hsp70 were found to enhance the proliferation and cytokine production of human antigen-specific CD4+ T cells. This was demonstrated in proliferation experiments using human monocytes as APC. Proliferated antigen-specific cells were detected combining HLA-DRB1*0401 or HLA-DRB1*1101 tetramer and CFSE staining. Treating monocytes with CD91 siRNA diminished these effects. Additional blocking of SR by the SR ligand fucoidan completely abolished enhanced proliferation and production of Th1 and Th2 cytokines. Taken together, our data indicate that in the human system, CD91 and members of the SR family efficiently direct Hsp70:peptide complexes into the MHC class II presentation pat... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3295321 Mon, 25 Jan 2010 00:00:00 +0100 3295321 http://www.medworm.com/index.php?rid=3213319&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20101613%26dopt%3DAbstract Authors: Imai T, Shen J, Chou B, Duan X, Tu L, Tetsutani K, Moriya C, Ishida H, Hamano S, Shimokawa C, Hisaeda H, Himeno K In developing malaria vaccines, the most crucial step is to elucidate the mechanisms involved in protective immunity against the parasites. We found that CD8(+) T cells contribute to protective immunity against infection with blood-stage parasites of Plasmodium yoelii. Infection of C57BL/6 mice with P. yoelii 17XL was lethal, while all mice infected with a low-virulence strain of the parasite 17XNL acquired complete resistance against re-infection with P. yoelii 17XL. However, the host mice transferred with CD8(+) T cells from mice primed only with P. yoelii17XNL failed to acquire protective immunity. On the other hand, the irradiated host mice were completely resi... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3213319 Mon, 25 Jan 2010 00:00:00 +0100 3213319 http://www.medworm.com/index.php?rid=3213318&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20101614%26dopt%3DAbstract Authors: Nunomura S, Gon Y, Yoshimaru T, Kashiwakura J, Kawakami T, Ra C Simultaneous stimulation with antigen and adenosine in mast cells induces a synergistic degranulation response at an low antigen dose that is insufficient to cause secretion by itself. This kind of stimulation is thought to be relevant to the immediate asthmatic response upon bronchial challenge with low-dose allergen. In this context, FcepsilonRI- and adenosine receptor-mediated signalings cooperate to increase degranulation in mast cells. In the present study, we prepared mast cells, which have mutations (Y219F/Y225F/Y229F) in three tyrosine residues of the FcepsilonRI beta-chain (FcRbeta)-ITAM, to elucidate the molecular mechanisms of degranulation response synergistically elicited by costimulation with low-dos... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3213318 Mon, 25 Jan 2010 00:00:00 +0100 3213318 http://www.medworm.com/index.php?rid=3213317&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20101615%26dopt%3DAbstract In this study, antigenic peptides from tetanus toxin and influenza hemagglutinin complexed to human stress-inducible Hsp70 were found to enhance the proliferation and cytokine production of human antigen-specific CD4(+) T cells. This was demonstrated in proliferation experiments using human monocytes as APC. Proliferated antigen-specific cells were detected combining HLA-DR tetramer and CFSE staining. Treating monocytes with CD91 siRNA diminished these effects. Additional blocking of scavenger receptors by the SR ligand fucoidan completely abolished enhanced proliferation and production of Th1 and Th2 cytokines. Taken together, our data indicate that in the human system, CD91 and members of the scavenger receptor family efficiently direct Hsp70:peptide complexes into the MHC class II prese... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3213317 Mon, 25 Jan 2010 00:00:00 +0100 3213317 http://www.medworm.com/index.php?rid=3213316&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20101616%26dopt%3DAbstract Authors: Kallal LE, Schaller MA, Lindell DM, Lira SA, Lukacs NW Chemokines are important mediators of the immune response to pathogens, but can also promote chronic inflammatory states. Chemokine receptor 6 (CCR6) is found on immature dendritic cells and effector/memory T cells, and binds a single ligand, CCL20, with high affinity. Here we investigated the role of CCL20 and CCR6 in a pulmonary viral infection caused by respiratory syncytial virus (RSV), a ubiquitous virus that can cause severe pulmonary complications. Neutralization of CCL20 during RSV infection significantly reduced lung pathology and favored a Th1 effector response. CCR6-deficient animals recapitulated this phenotype, and additionally showed enhanced viral clearance when compared to WT mice. No differences were obser... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3213316 Mon, 25 Jan 2010 00:00:00 +0100 3213316 http://www.medworm.com/index.php?rid=3213315&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20101617%26dopt%3DAbstract Authors: Janke M, Peine M, Nass A, Morawietz L, Hamann A, Scheffold A Recently, IL-17 produced by Th17 cells was described as pro-inflammatory cytokine with an eminent role in autoimmune diseases, e.g. rheumatoid arthritis. The lack of IL-17 leads to amelioration of collagen-induced arthritis. IL-17 induction in naïve CD4+ T cells depends on IL-6 and TGF-beta and is enhanced by IL-23. However, the in vivo inflammatory potential of in vitro-primed Th17 cells remains unclear. Here, we show that, although IL-17 neutralisation results in amelioration of murine ovalbumin-induced arthritis, in vitro-primed Th17 cells cannot exacerbate arthritic symptoms after adoptive transfer. Furthermore, Th17 cells cannot induce an inflammatory DTH reaction because they fail to migrate into inflamed ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3213315 Mon, 25 Jan 2010 00:00:00 +0100 3213315 http://www.medworm.com/index.php?rid=3213314&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20101618%26dopt%3DAbstract In this study we showed that immature viable DC have the ability to uptake apoptotic DC as well as necrotic DC without it being recognized as an inflammatory event by immature viable DC. However, the specific uptake of apoptotic DC converted immature viable DC into tolerogenic DC, which were resistant to LPS induced maturation. In contrast, these tolerogenic DC secreted increased levels of TGF-â1, which induced differentiation of naïve T cells into Foxp3(+) regulatory T cells (Treg). Furthermore, induction of Treg differentiation only occurred upon uptake of apoptotic DC and not upon uptake of apoptotic splenocytes by viable DC, indicating that it is specifically the uptake of apoptotic DC that gives viable immature DC the potential to induce Foxp3(+) Treg. Taken together, these ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3213314 Mon, 25 Jan 2010 00:00:00 +0100 3213314 http://www.medworm.com/index.php?rid=3213313&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20101619%26dopt%3DAbstract Authors: Ishiura N, Nakashima H, Watanabe R, Kuwano Y, Adachi T, Takahashi Y, Tsubata T, Okochi H, Tamaki K, Tedder TF, Fujimoto M CD19 is a B-cell transmembrane molecule that is critical for B cell activation. CD19 serves as a scaffold protein for key signal transduction molecules including Lyn, PI3K, and Vav, by providing docking sites for these molecules via phosphorylation of CD19-Y(513), CD19-Y(482), and CD19-Y(391). We investigated the process of CD19 tyrosine phophorylation during B cell activation using antibodies specific for each of these phosphorylated tyrosines. BCR engagement induced differential tyrosine phosphorylation, as CD19-Y(513) phophorylation occurred first, and CD19-Y(482) phosphorylation was delayed and transient. Different BCR isotypes exhibited distinct patter... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3213313 Mon, 25 Jan 2010 00:00:00 +0100 3213313 http://www.medworm.com/index.php?rid=3179596&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939527 IL-35 is a heterodimer of EBV-induced gene 3 and of the p35 subunit of IL-12, and recently identified as an inhibitory cytokine produced by natural Treg in mice, but not in humans. Here we demonstrate that DC activated by human rhinoviruses (R-DC) induce IL-35 production and release, as well as a suppressor function in CD4+ and CD8+ T cells derived from human peripheral blood but not in naïve T cells from cord blood. The induction of IL-35-producing T cells by R-DC was FOXP3-independent, but blocking of B7-H1 (CD274) and sialoadhesin (CD169) on R-DC with mAb against both receptors prevented the induction of IL-35. Thus, the combinatorial signal delivered by R-DC to T cells via B7-H1 and sialoadhesin is crucial for the induction of human IL-35+ Treg. These results demonstrate a novel pathw... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3179596 Sun, 17 Jan 2010 00:00:00 +0100 3179596 http://www.medworm.com/index.php?rid=3189719&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20082358%26dopt%3DAbstract Authors: Deenick EK, Elford AR, Pellegrini M, Hall H, Mak TW, Ohashi PS Regulatory T (Treg) cells are crucial for maintaining peripheral tolerance and controlling T cell responses. The generation of Treg in the thymus requires TCR triggering and CD28 costimulation. Engagement of these receptors induces a number of signalling pathways, including the activation of NF-kappaB via PKCtheta and the Bcl-10/CARMA1/MALT complex. Previous studies have shown that PKCtheta, Bcl-10 and CARMA1 are important for Treg development. It is unclear, however, whether different members of the NF-kappaB family contribute to Treg development or homeostasis. Here we show that Treg numbers are reduced in the absence of c-Rel but not NF-kappaB1 (p50). Furthermore, using mixed bone marrow chimeras from wild type ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3189719 Fri, 15 Jan 2010 00:00:00 +0100 3189719 http://www.medworm.com/index.php?rid=3360084&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939661 The capacity of immature B cells of the spleen and bone marrow to differentiate in vitro into cells representing mature end stage cells was investigated using B-cell activating factor belonging to the TNF family (BAFF) and Notch pathway activators. Immature splenic and bone marrow B cells were found, in the presence of both of these activators, to mature into cells with follicular mature (FM) and marginal zone (MZ) cell phenotypes. Such cells were functionally responsive to B-cell-specific activation. The derivation in vitro of cells with an MZ phenotype was more robust from CD23- populations than CD23+ immature/transitional B cells, suggesting a direct immature/T1 B cell to MZ cell differentiation pathway. Transcript analysis of the in vitro-derived B-cell populations demonstrated express... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3360084 Wed, 13 Jan 2010 00:00:00 +0100 3360084 http://www.medworm.com/index.php?rid=3179597&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939566 The objective of this study was to examine the affect of Natura-[alpha], a newly developed cytokine regulator, on CIA and on Th cell development. Natura-[alpha] treatment was administered before or during arthritis induction. Anti-type II collagen antibodies and cytokine expression were evaluated by ELISA. Emergence of CD4+CD25+Foxp3+ T cells was assessed by flow cytometry. Th-17 differentiation of naive CD4 T cells was assessed in cultures with anti-CD3 and anti-CD28. We showed that Natura-[alpha] both prevented and treated CIA. We further demonstrated that in vivo treatment with Natura-[alpha] inhibited IL-17 production and anti-type II collagen IgG development. We showed in vitro, using an APC-free system, that Natura-[alpha] acted directly on differentiating T cells and inhibiting the ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3179597 Wed, 13 Jan 2010 00:00:00 +0100 3179597 http://www.medworm.com/index.php?rid=3179456&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20077403%26dopt%3DAbstract The objective of this study was to examine the affect of Natura-alpha, a newly developed cytokine regulator, on CIA and on Th cell development. Natura-alpha treatment was administered before or during arthritis induction. Anti-type II collagen and cytokine expression were evaluated by ELISA. Emergence of CD4+CD25+Foxp3+T cells was assessed by flow cytometry. Th-17 differentiation of naive CD4 T cells was assessed in cultures with anti-CD3 and anti-CD28. We showed that Natura-alpha both prevented and treated CIA. We further demonstrated that in vivo treatment with Natura-alpha inhibited IL-17 production and anti-type II collagen IgG development. We showed in vitro, using an APC-free system, that Natura-alpha acted directly on differentiating T cells and inhibiting the formation of Th-1 and ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3179456 Wed, 13 Jan 2010 00:00:00 +0100 3179456 http://www.medworm.com/index.php?rid=3179455&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20077404%26dopt%3DAbstract Authors: Roundy KM, Jacobson AC, Weis JJ, Weis JH The capacity of immature B cells of the spleen and bone marrow to differentiate in vitro into cells representing mature end stage cells was investigated using BAFF and Notch pathway activators. Immature splenic and bone marrow B cells were found, in the presence of both of these activators, to mature into cells with follicular mature (FM) and marginal zone (MZ) cell phenotypes. Such cells were functionally responsive to B-cell-specific activation. The derivation in vitro of cells with a MZ phenotype was more robust from CD23- populations than CD23+ immature/transitional B cells suggesting a direct immature/T1 B cell to MZ cell differentiation pathway. Transcript analysis of the in vitro derived B cell populations demonstrated expression... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3179455 Wed, 13 Jan 2010 00:00:00 +0100 3179455 http://www.medworm.com/index.php?rid=3179454&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20077405%26dopt%3DAbstract Authors: Frebel H, Richter K, Oxenius A Persistent viral infections are, by definition, associated with ineffective antiviral immunity, in particular those infections caused by viruses that are highly productive and replicative (including HIV, HBV and HCV). The reasons for ineffective antiviral immunity in these types of infections are complex and manifold, and only recently a more comprehensive picture of the parameters responsible for attenuation of immune function is emerging. One reason for poor viral control in these types of infections is the functional deterioration of antiviral T-cell responses and understanding the underlying mechanisms is of key importance. This review summarizes our current knowledge of cell-intrinsic and cell-extrinsic parameters that contribute to T-cell e... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3179454 Wed, 13 Jan 2010 00:00:00 +0100 3179454 http://www.medworm.com/index.php?rid=3164779&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20063313%26dopt%3DAbstract This study investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum-parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children's in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD4(+)CD25(hi)FOXP3(+) T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminth-uninfected groups: Ag-specific proliferative responses increased upon CD4(+)CD25(hi) T-cell depletion in geohelminth-infected subjects only. In addition, IFN-gamma production in response to both BCG and parasitized RBC was increased after removal of CD4(+)CD25(hi) T cells. These data demonstrate that geohelm... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3164779 Fri, 08 Jan 2010 00:00:00 +0100 3164779 http://www.medworm.com/index.php?rid=3154071&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939699 This study investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum-parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children's in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD4+CD25hiFOXP3+ T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminth-uninfected groups: Ag-specific proliferative responses increased upon CD4+CD25hi T-cell depletion in geohelminth-infected subjects only. In addition, IFN-[gamma] production in response to both BCG and parasitized RBC was increased after removal of CD4+CD25hi T cells. These data demonstrate that geohelminth-associa... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3154071 Fri, 08 Jan 2010 00:00:00 +0100 3154071 http://www.medworm.com/index.php?rid=3150058&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939798 Rapidly induced, specific Ab generated in extrafollicular foci are important components of early immune protection to influenza virus. The signal(s) that prompt B cells to participate in extrafollicular rather than germinal center responses are incompletely understood. To study the regulation of early B-cell differentiation events following influenza infection, we exploited earlier findings of a strong contribution of C12 idiotype-expressing B cells to the primary HA-specific response against influenza A/PR/8/34. Using an idiotype-specific mAb to C12 and labeled HA, in conjunction with multicolor flow cytometry, we followed the fate of C12Id-expressing influenza HA-specific B cells in WT BALB/c mice, requiring neither genetic manipulation nor adoptive cell transfer. Our studies demonstrate... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3150058 Fri, 08 Jan 2010 00:00:00 +0100 3150058 http://www.medworm.com/index.php?rid=3263696&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939842 T-cell immunoglobulin, mucin domain-3 (Tim-3) is a membrane protein expressed at late stages of IFN-[gamma] secreting CD4+ Th1 cell differentiation and constitutively on DC. Ligation of Tim-3 on Th1 cells terminates Th1 immune responses. In addition, Tim-3 plays a role in tolerance induction, although the mechanism by which this is accomplished has yet to be elucidated. While it is clear that Tim-3 plays an important role in the immune system, little is known regarding the molecular pathways that regulate Tim-3 expression. In the current study, we examine the role of Th1-associated transcription factors in regulating Tim-3 expression. Our experiments reveal that Tim-3 expression is regulated by the Th1-specific transcription factor T-bet. This introduces a novel paradigm into the generatio... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3263696 Mon, 04 Jan 2010 00:00:00 +0100 3263696 http://www.medworm.com/index.php?rid=3225345&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939706 Occlusive transplant vasculopathy (TV) is the major cause for chronic graft rejection. Since endothelial cells (EC) are the first graft cells encountered by activated host lymphocytes, it is important to delineate the molecular mechanisms that coordinate the interaction of EC with activated T cells. Here, the interaction of CD8+ T cells with Ag-presenting EC in vivo was examined using a transgenic heart transplantation model with [beta]-galactosidase ([beta]-gal) expression exclusively in EC (Tie2-LacZ hearts). We found that priming with [beta]-gal peptide-loaded DC failed to generate a strong systemic IFN-[gamma] response, but elicited pronounced TV in both IFN-[gamma] receptor (IFNGR)-competent, and ifngr-/- Tie2-LacZ hearts. In contrast, stimulation of EC-specific CD8+ T cells with [bet... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225345 Mon, 04 Jan 2010 00:00:00 +0100 3225345 http://www.medworm.com/index.php?rid=3149559&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20049875%26dopt%3DAbstract Authors: Bolinger B, Engeler D, Krebs P, Miller S, Firner S, Hoffmann M, Palmer DC, Restifo NP, Tian Y, Clavien PA, Ludewig B Occlusive transplant vasculopathy (TV) is the major cause for chronic graft rejection. Since endothelial cells (ECs) are the first graft cells encountered by activated host lymphocytes, it is important to delineate the molecular mechanisms that coordinate the interaction of ECs with activated T cells. Here, the interaction of CD8(+) T cells with antigen-presenting ECs in vivo was examined using a transgenic heart transplantation model with beta-galactosidase (beta-gal) expression exclusively in ECs (Tie2-LacZ hearts). We found that priming with beta-gal peptide-loaded dendritic cells failed to generate a strong systemic IFN-gamma response, but elicited pronounce... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3149559 Mon, 04 Jan 2010 00:00:00 +0100 3149559 http://www.medworm.com/index.php?rid=3149558&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20049876%26dopt%3DAbstract Authors: Anderson AC, Lord GM, Dardalhon V, Lee DH, Sabatos CA, Glimcher LH, Kuchroo VK Tim-3 (T cell immunoglobulin, mucin domain)-3 is a membrane protein expressed at late stages of IFN-gamma secreting CD4(+) T helper type 1 (Th1) cell differentiation and constitutively on dendritic cells (DC). Ligation of Tim-3 on Th1 cells terminates Th1 immune responses. In addition, Tim-3 plays a role in tolerance induction, though the mechanism by which this is accomplished has yet to be elucidated. While it is clear that Tim-3 plays an important role in the immune system, little is known regarding the molecular pathways that regulate Tim-3 expression. In the current study, we examine the role of Th1-associated transcription factors in regulating Tim-3 expression. Our experiments reveal that Tim... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3149558 Mon, 04 Jan 2010 00:00:00 +0100 3149558 http://www.medworm.com/index.php?rid=3149557&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20049877%26dopt%3DAbstract Authors: Visekruna A, Huber M, Hellhund A, Bothur E, Reinhard K, Bollig N, Schmidt N, Joeris T, Lohoff M, Steinhoff U The NF-kappaB/Rel family member c-Rel was described to be required for the development of T(H)1 responses. However, the role of c-Rel in the differentiation of T(H)17 and regulatory CD4(+) Foxp3(+) T (Treg) cells remains obscure. Here, we show that in the absence of c-Rel, in vitro differentiation of pro-inflammatory T(H)17 cells is normal. In contrast, generation of inducible Treg (iTreg) within c-Rel deficient CD4(+) T cells was severely hampered and correlated to reduced numbers of Foxp3(+) T cells in vivo. Mechanistically, in vitro conversion of naïve CD4(+) T cells into iTreg cells was crucially dependent on c-Rel-mediated synthesis of endogenous IL-2. The add... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3149557 Mon, 04 Jan 2010 00:00:00 +0100 3149557 http://www.medworm.com/index.php?rid=3136048&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20043288%26dopt%3DAbstract Authors: Takahama Y, Miyasaka M PMID: 20043288 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3136048 Wed, 30 Dec 2009 00:00:00 +0100 3136048 http://www.medworm.com/index.php?rid=3136047&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20043289%26dopt%3DAbstract Authors: PMID: 20043289 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3136047 Wed, 30 Dec 2009 00:00:00 +0100 3136047 http://www.medworm.com/index.php?rid=3136046&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20043290%26dopt%3DAbstract Authors: Palker TJ, Dong G, Leitner WW In June 2009, the National Institute of Allergy and Infectious Diseases (NIAID), Division of Allergy, Immunology and Transplantation (DAIT), sponsored a workshop entitled Mast Cells in Innate and Adaptive Immunity. International experts in mast cell biology discussed recent advances in the field and future areas of research aimed at advancing our understanding of the importance of mast cells in shaping nonallergic, adaptive immunity to infection. PMID: 20043290 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3136046 Wed, 30 Dec 2009 00:00:00 +0100 3136046 http://www.medworm.com/index.php?rid=3136045&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20043291%26dopt%3DAbstract Authors: Tangye SG, Tarlinton DM PMID: 20043291 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3136045 Wed, 30 Dec 2009 00:00:00 +0100 3136045 http://www.medworm.com/index.php?rid=3136044&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20043292%26dopt%3DAbstract Authors: COVER IMAGE: This issue's cover image shows immunofluorescent staining of endothelial cells for microtubules (red) and vascular endothelial cadherin (green). The image was taken from the article Endothelial IQGAP1 regulates efficient lymphocyte transendothelial migration by Nakhaei-Nejad et al. (pp. 204-213), in which the authors examine the role of IQGAP1, an adaptor protein that binds to filamentous-actin and microtubules at interendothelial junctions, during lymphocyte transendothelial migration. IT PAYS TO HAVE AN IMMUNE MOTHER: pp. 113-116Currently, the archaic fear of a circulating, possibly deadly infection has raised its head in the form of H1N1 influenza. Although we have learned how to artificially vaccinate against influenza and many other infectious agents, we sti... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3136044 Wed, 30 Dec 2009 00:00:00 +0100 3136044 http://www.medworm.com/index.php?rid=3136043&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20043293%26dopt%3DAbstract Authors: PMID: 20043293 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3136043 Wed, 30 Dec 2009 00:00:00 +0100 3136043 http://www.medworm.com/index.php?rid=3136042&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20043294%26dopt%3DAbstract Authors: PMID: 20043294 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3136042 Wed, 30 Dec 2009 00:00:00 +0100 3136042 http://www.medworm.com/index.php?rid=3263694&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939889 Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions, mimicked by the combined action of LPS and IFN-[gamma] (M1 polarization). However, macrophages can undergo an alternative type of activation stimulated by Th2 cytokines, and acquire a role in cell growth and tissue repair control (M2 polarization). We characterized the expression of genes related to iron homeostasis in fully differentiated unpolarized (M0), M1 and M2 human macrophages. The molecular signature of the M1 macrophages showed changes in gene expression (ferroportin repression and H ferritin induction) that favour iron sequestration in the reticuloendothelial system, a hallmark of inflammatory disorders, whereas the M2 macrophages had an expression profil... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3263694 Mon, 28 Dec 2009 00:00:00 +0100 3263694 http://www.medworm.com/index.php?rid=3263693&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939755 Missing-self-reactivity can be mimicked by blocking self-specific inhibitory receptors on NK cells, leading to increased rejection of syngeneic tumor cells. Using a mouse model, we investigated whether Ab-mediated blocking of inhibitory receptors, to a degree where NK cells rejected syngeneic tumor cells, would still allow self-tolerance toward normal syngeneic cells. Ly49C/I inhibitory receptors on C57BL/6 (H-2b) NK cells were blocked with F(ab')2 fragments of the mAb 5E6. Inhibitory receptor blockade in vivo caused rejection of i.v. inoculated fluorescence-labeled syngeneic lymphoma line cells but not of syngeneic spleen cells, BM cells or lymphoblasts. The selective rejection of tumor cells was NK cell-dependent and specifically induced by Ly49C/I blockade. Moreover, selective tumor rej... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3263693 Mon, 28 Dec 2009 00:00:00 +0100 3263693 http://www.medworm.com/index.php?rid=3263692&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939638 Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria-specific FOXP3+ Treg and more generalized FOXP3+ CD4+ Treg in chronic and resolved PM, alongside increased Th1 pro-inflam... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3263692 Mon, 28 Dec 2009 00:00:00 +0100 3263692 http://www.medworm.com/index.php?rid=3263691&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939468 The CD300e surface molecule, originally termed immune receptor expressed by myeloid cells (IREM)-2, was reported to associate with the DNAX-activating protein (DAP) 12 adaptor in co-transfected cells, and is capable of signaling. In the present report, we investigated in detail the function of CD300e in monocytes and myeloid DC (mDC) freshly isolated from peripheral blood of normal blood donors. Upon engagement by an agonistic mAb, CD300e triggered an intracellular calcium mobilization and superoxide anion O2- production in monocytes. Activation via CD300e provided survival signals that prevented monocyte and mDC apoptosis, triggered the production of pro-inflammatory cytokines and upregulated the expression of cell surface co-stimulatory molecules in both cell types. Moreover, CD300e acti... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3263691 Mon, 28 Dec 2009 00:00:00 +0100 3263691 http://www.medworm.com/index.php?rid=3225358&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939857 This study demonstrates a vaccine strategy to generate high-avidity CTL responses that can be used in anti-tumor and anti-viral vaccine settings. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225358 Mon, 28 Dec 2009 00:00:00 +0100 3225358 http://www.medworm.com/index.php?rid=3225354&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939992 CRX-527 belongs to a new family of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates, which are considered as potential vaccine adjuvants or stand-alone immunotherapeutics to harness innate immune defenses. Since natural lipid A from bacterial LPS depends on membrane-bound (mCD14) or soluble CD14 for its TLR4 ligand activity, we investigated the involvement of both forms of CD14 in the responses elicited by CRX-527. First, we found that CRX-527 induces NF-[kappa]B and interferon regulatory factor-3 (IRF-3) activation in human embryonic kidney cells transfected with TLR4 and MD-2 genes alone, whereas the responses to LPS require either co-transfection of the gene encoding mCD14 or addition of soluble CD14. We then observed that monocyte-derived DC, which are devoid of mC... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225354 Mon, 28 Dec 2009 00:00:00 +0100 3225354 http://www.medworm.com/index.php?rid=3225353&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939613 Depletion of CD4+CD25+FoxP3+ Treg using PC61 mAb (anti-murine CD25 rat IgG1) is widely used to characterize Treg function in vivo. However, the mechanism of Treg depletion remains largely unknown. Herein, we report the PC61 mAb's mechanism of action. In peripheral blood, a single injection of PC61 mAb eliminated [sim]70% of CD4+FoxP3+ cells with the remaining Treg expressing low or no CD25. Functional blockade of Fc[gamma] receptors with 2.4G2 mAb significantly inhibited PC61 mAb activity. Furthermore, Fc[gamma] receptor (Fc[gamma]R)III-/- mice were resistant to Treg depletion. Fc[gamma]RIII is expressed on immune cells including NK cells and macrophages that are the major effector cells for Ab-dependent-cellular-cytotoxicity and Ab-dependent-cellular-phagocytosis, respectively. Depletion ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225353 Mon, 28 Dec 2009 00:00:00 +0100 3225353 http://www.medworm.com/index.php?rid=3225352&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939646 This study demonstrates that engagement of CD154 in Jurkat D1.1 cells with soluble CD40 leads to PKC [alpha] and [delta] activation, calcium mobilization, and phosphorylation of the Map kinases ERK1/2 and p38. Such response is accompanied by significant recruitment of CD154 into lipid rafts. Disruption of lipid rafts integrity with nystatin or methyl [beta]-cyclodextrin abrogated PKC[alpha] PKC[delta] and p38 phosphorylation, but had no effect on ERK1/2 phosphorylation. Inhibition of PKC activation completely abolished p38 phosphorylation but had no effect on ERK1/2 phosphorylation, suggesting that localization of CD154 within lipid rafts is an absolute requirement for CD154-induced PKC[alpha]- and PKC[delta]-dependent p38 phosphorylation. Furthermore, CD154 acts as co-stimulator for the p... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225352 Mon, 28 Dec 2009 00:00:00 +0100 3225352 http://www.medworm.com/index.php?rid=3225347&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200838951 In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-[kappa]B-dependent blockage. (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225347 Mon, 28 Dec 2009 00:00:00 +0100 3225347 http://www.medworm.com/index.php?rid=3225344&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939858 During B-cell development, immature B-cell fate is determined by whether the BCR is engaged in the bone marrow. Immature B cells that are non-autoreactive continue maturation and emigrate from the marrow, whereas autoreactive immature B cells remain and are tolerized. However, the microenvironment where these events occur and the chemoattractants responsible for immature B-cell trafficking within and out of the bone marrow remain largely undefined. Sphingosine 1-phosphate (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte egress and in this study we investigated whether S1P contributes to B-cell development, egress and positioning within the bone marrow. Our findings show that immature B cells are chemotactic toward S1P but that this response is dependent on Ag re... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225344 Mon, 28 Dec 2009 00:00:00 +0100 3225344 http://www.medworm.com/index.php?rid=3130276&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039295%26dopt%3DAbstract In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-kappaB-dependent blockage. PMID: 20039295 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130276 Mon, 28 Dec 2009 00:00:00 +0100 3130276 http://www.medworm.com/index.php?rid=3130275&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039296%26dopt%3DAbstract Authors: Brckalo T, Calzetti F, Pérez-Cabezas B, Borràs FE, Cassatella MA, López-Botet M The CD300e surface molecule, originally termed immune receptor expressed by myeloid cells-2 (IREM-2), was reported to associate with the DAP12 adaptor in co-transfected cells, and is capable of signaling. In the present report, we investigated in detail the function of CD300e in monocytes and myeloid dendritic cells (mDC) freshly-isolated from peripheral blood of normal blood donors. Upon engagement by an agonistic mAb, CD300e triggered an intracellular calcium mobilization and superoxide anion production in monocytes. Activation via CD300e provided survival signals that prevented monocyte and mDC apoptosis, triggered the production of pro-inflammatory cytokines and up-regulated the ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130275 Mon, 28 Dec 2009 00:00:00 +0100 3130275 http://www.medworm.com/index.php?rid=3130274&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039297%26dopt%3DAbstract Authors: Setiady YY, Coccia JA, Park PU Depletion of CD4+CD25+Foxp3+ regulatory T cells (Tregs) using PC61 monoclonal antibody (mAb) (anti-murine CD25 rat IgG1) is widely used to characterize Treg function in vivo. However, the mechanism of Treg depletion remains largely unknown. Herein, we report the PC61 mAb's mechanism of action. In peripheral blood, a single injection of PC61 mAb eliminated approximately 70% of CD4+Foxp3+ cells with the remaining Tregs expressing low or no CD25. Functional blockade of Fc gamma receptors with 2.4G2 mAb significantly inhibited PC61 mAb activity. Furthermore, Fc gamma RIII-/- mice were resistant to Treg depletion. Fc gamma RIII is expressed on immune cells including NK cells and macrophages which are the major effector cells for antibody-dependent-cel... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130274 Mon, 28 Dec 2009 00:00:00 +0100 3130274 http://www.medworm.com/index.php?rid=3130273&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039298%26dopt%3DAbstract Authors: Flanagan KL, Halliday A, Burl S, Landgraf K, Jagne YJ, Noho-Konteh F, Townend J, Miles DJ, van der Sande M, Whittle H, Rowland-Jones S Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign antigens. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analysed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial antigens in ute... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130273 Mon, 28 Dec 2009 00:00:00 +0100 3130273 http://www.medworm.com/index.php?rid=3130272&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039299%26dopt%3DAbstract Authors: Fakhry YE, Alturaihi H, Diallo D, Merhi Y, Mourad W Although signal pathways triggered via the CD40 molecule are well characterized, those induced via CD154 are less known. The present study demonstrates that engagement of CD154 in Jurkat D1.1 cells with soluble CD40 leads to protein kinase C (PKC) alpha and delta activation, calcium mobilization, and phosphorylation of the Map kinases ERK1/2 and p38. Such response is accompanied by significant recruitment of CD154 into lipid rafts. Disruption of lipid rafts integrity with nystatin or MbetaCD abrogated PKCalpha, PKCdelta and p38 phosphorylation, but had no effect on ERK1/2 phosphorylation. Inhibition of PKC activation completely abolished p38 phosphorylation but had no effect on ERK1/2 phosphorylation, suggesting that localiza... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130272 Mon, 28 Dec 2009 00:00:00 +0100 3130272 http://www.medworm.com/index.php?rid=3130271&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039300%26dopt%3DAbstract Authors: Vahlne G, Lindholm K, Meier A, Wickström S, Lakshmikanth T, Brennan F, Wilken M, Nielsen R, Romagné F, Wagtmann NR, Kärre K, Johansson MH Missing-self-reactivity can be mimicked by blocking self-specific inhibitory receptors on NK cells, leading to increased rejection of syngeneic tumour cells. Using a mouse model, we investigated whether antibody-mediated blocking of inhibitory receptors, to a degree where NK cells rejected syngeneic tumour cells, would still allow self-tolerance towards normal syngeneic cells. Ly49C/I inhibitory receptors on C57BL/6 (H-2(b)) NK cells were blocked with F(ab')(2) fragments of the monoclonal antibody 5E6. Inhibitory receptor blockade in vivo caused rejection of i.v. inoculated fluorescence-labelled syngeneic lymphoma line cells b... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130271 Mon, 28 Dec 2009 00:00:00 +0100 3130271 http://www.medworm.com/index.php?rid=3130270&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039301%26dopt%3DAbstract This study demonstrates a vaccine strategy to generate high avidity CTL responses that can be used in anti-tumor and anti-viral vaccine settings. PMID: 20039301 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130270 Mon, 28 Dec 2009 00:00:00 +0100 3130270 http://www.medworm.com/index.php?rid=3130269&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039302%26dopt%3DAbstract Authors: Donovan EE, Pelanda R, Torres RM During B cell development, immature B cell fate is determined by whether the B cell antigen receptor is engaged in the bone marrow. Immature B cells that are non-autoreactive continue maturation and emigrate from the marrow whereas autoreactive immature B cells remain and are tolerized. However, the microenvironment where these events occur and the chemoattractants responsible for immature B cell trafficking within and out of the bone marrow remain largely undefined. Sphingosine 1-phosphate (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte egress and in this study we investigated whether S1P contributed to B cell development, egress and positioning within the bone marrow. Our findings show that immature B cells are ch... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130269 Mon, 28 Dec 2009 00:00:00 +0100 3130269 http://www.medworm.com/index.php?rid=3130268&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039303%26dopt%3DAbstract Authors: Recalcati S, Locati M, Marini A, Santambrogio P, Zaninotto F, De Pizzol M, Zammataro L, Girelli D, Cairo G Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions, mimicked by the combined action of LPS and IFNgamma (M1 polarization). However, macrophages can undergo an alternative type of activation stimulated by Th2 cytokines, and acquire a role in cell growth and tissue repair control (M2 polarization). We characterised the expression of genes related to iron homeostasis in fully differentiated unpolarized (M0), M1 and M2 human macrophages. The molecular signature of the M1 macrophages showed changes in gene expression (ferroportin repression and H ferritin induction) that favour iron sequestration in the ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130268 Mon, 28 Dec 2009 00:00:00 +0100 3130268 http://www.medworm.com/index.php?rid=3130267&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039304%26dopt%3DAbstract We describe the expression of all four known adenosine receptors A1R, A2aR, A2bR, and A3R, on mouse iNKT cells. We show that IL-4 production in primary mouse iNKT cells and a human iNKT line is efficiently inhibited by A2aR blockade with an inverse relation to IL-4. These data are supported by A2aR-deficient mice, which exhibit largely decreased levels of IL-4, IL-10 and TGF-beta concomitantly with an increase of IFN-gamma upon alpha-GalCer administration in vivo. While A2aR inhibits other lymphocyte populations, A2aR is required for the secretion of IL-4 and IL-10 by iNKT cells. These data suggest adenosine:A2aR-mediated mechanisms can control the cytokine secretion pattern of iNKT cells. PMID: 20039304 [PubMed - as supplied by publisher] (Source: European Journal of Immunology) European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130267 Mon, 28 Dec 2009 00:00:00 +0100 3130267 http://www.medworm.com/index.php?rid=3130266&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039305%26dopt%3DAbstract Authors: Legat A, Thomas S, Hermand P, Van Mechelen M, Goldman M, De Wit D CRX-527 belongs to a new family of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates, which are considered as potential vaccine adjuvants or stand-alone immunotherapeutics to harness innate immune defences. Since natural lipid A from bacterial LPS depends on membrane-bound (mCD14) or soluble CD14 (sCD14) for its TLR4 ligand activity, we investigated the involvement of both forms of CD14 in the responses elicited by CRX-527. First, we found that CRX-527 induces NF-kappaB and IRF-3 (interferon regulatory factor-3) activation in HEK cells transfected with TLR4 and MD-2 genes alone, whereas the responses to LPS require either co-transfection of the gene encoding mCD14 or addition of sCD14. We the... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130266 Mon, 28 Dec 2009 00:00:00 +0100 3130266 http://www.medworm.com/index.php?rid=3130265&cid=s_33627_3_f&fid=33855&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20039306%26dopt%3DAbstract Authors: Mowat AM There is almost no aspect of the immune response that is not regulated by toll-like receptors (TLR). Initially described as drivers of the innate immune response to pathogens, it is now clear that the TLR family can also influence most aspects of adaptive immunity, as well as determine how tissue cells interact with microbes in their environment. In particular, the intestine and its immune system must co-exist with an enormous community of commensal bacteria and are also on constant alert against invading pathogens. Unsurprisingly there is therefore great interest in how TLR might regulate physiological and pathological reactions in the gut. A paper in this issue of the European Journal of Immunology addresses this question with some elegant experiments that indicate ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3130265 Mon, 28 Dec 2009 00:00:00 +0100 3130265 http://www.medworm.com/index.php?rid=3225357&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939761 In this study, we assessed EBV-specific humoral and cellular immune responses in the cerebrospinal fluid (CSF) of patients with early MS, other inflammatory neurological diseases (OIND) and non-inflammatory neurological diseases (NIND). The neurotropic herpesvirus CMV served as a control. Virus-specific humoral immune responses were assessed in 123 consecutive patients and the intrathecal recruitment of virus-specific antibodies was expressed as antibody indexes. Cellular immune responses tested in the blood of 55/123 patients were positive in 46/55. The CD8+ CTL responses of these 46 patients were assessed in the blood and CSF using a CFSE-based CTL assay. We found that viral capsid antigen and EBV-encoded nuclear antigen-1, but not CMV IgG antibody indexes, were increased in early MS as ... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225357 Wed, 16 Dec 2009 00:00:00 +0100 3225357 http://www.medworm.com/index.php?rid=3225355&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939488 We have shown previously that cytokines IL-4 and IL-13 induce protection in porcine vascular endothelial cells (EC) against killing by the membrane attack complex (MAC) of human complement. This protection is intrinsic, not due to changes in complement regulatory proteins, and requires activation of Akt and sterol receptor element binding protein-1 (SREBP-1), which regulates fatty acid and phospholipid synthesis. Here we report that, compared to EC incubated in medium, IL-4-treated EC had a profound reduction in complement-mediated ATP loss and in killing assessed by vital dye uptake, but only a slight reduction in permeability disruption measured by calcein release. While controls exposed to complement lost mitochondrial membrane potential and subsequently died, protected EC maintained mi... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225355 Wed, 16 Dec 2009 00:00:00 +0100 3225355 http://www.medworm.com/index.php?rid=3225351&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939724 Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2-skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox-active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL-13 and eotaxin production are decreased in TRX-Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2-type cytokines and Ig were detected in LN and serum, respectively, from TRX-Tg and WT mice. Likewise, CD4+ T cells from both strains of mice developed similar Th1... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225351 Wed, 16 Dec 2009 00:00:00 +0100 3225351 http://www.medworm.com/index.php?rid=3225350&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939747 In this study, we have identified a secreted 13 kDa lectin from Mtb (Mtb, Mycobacterium tuberculosis; sMTL-13) by homology search of a non-redundant lectin database. Bioinformatic analysis revealed that sMTL-13 belongs to the ricin-type [beta]-trefoil family of proteins containing a Sec-type signal peptide present in Mtb complex species, but not in non-tuberculous mycobacteria. Following heterologous expression of sMTL-13 and generation of an mAb (clone 276.B7/IgG1[kappa]), we confirmed that this lectin is present in culture filtrate proteins from Mtb H37Rv, but not in non-tuberculous mycobacteria-derived culture filtrate proteins. In addition, sMTL-13 leads to an increased IFN-[gamma] production by PBMC from active tuberculosis (ATB) patients. Furthermore, sera from ATB patients displayed... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225350 Wed, 16 Dec 2009 00:00:00 +0100 3225350 http://www.medworm.com/index.php?rid=3225349&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939865 In this study, we show that distinct mechanisms are responsible for the parenteral and mucosal adjuvanticity of LT. Indeed, the systemic administration of LT upregulates the expression of glucocorticoid-induced TNFR-related protein (GITR), but not other activation markers, in naive T cells. Using WT and GITR-deficient mice and LT and its enzymatically inactive mutant LTK63 as adjuvants, we show that the induction of GITR expression in T cells accounts for the systemic immunostimulatory capacity of LT, which requires an intact enzymatic activity. In contrast, the mucosal administration of LT does not induce GITR expression on Peyer's patche T cells and accordingly no differences are observed in the mucosal adjuvanticity of LT between WT and GITR-deficient mice. Altogether, our results demon... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225349 Wed, 16 Dec 2009 00:00:00 +0100 3225349 http://www.medworm.com/index.php?rid=3225346&cid=s_33627_3_f&fid=33627&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Feji.200939333 C5a is a proinflammatory mediator that has recently been shown to regulate adaptive immune responses. Here we demonstrate that C5a receptor (C5aR) signaling in DC affects the development of Treg and Th17 cells. Genetic ablation or pharmacological targeting of the C5aR in spleen-derived DC results in increased production of TGF-[beta] leading to de novo differentiation of Foxp3+ Treg within 12 h after co-incubation with CD4+ T cells from DO11.10/RAG2-/- mice. Stimulation of C5aR-/- DC with OVA and TLR2 ligand Pam3CSK4 increased TGF-[beta] production and induced high levels of IL-6 and IL-23 but only minor amounts of IL-12 leading to differentiation of Th cells producing IL-17A and IL-21. Th17 differentiation was also found in vivo after adoptive transfer of CD4+ Th cell into C5aR-/- mice im... European Journal of Immunology journals http://www.medworm.com/rss/comments.php?id=3225346 Wed, 16 Dec 2009 00:00:00 +0100 3225346