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 'International Immunology' source. Thu, 18 Mar 2010 13:39:26 +0100 http://www.medworm.com/index.php?rid=3307931&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F213-a%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3307931 Thu, 25 Feb 2010 23:28:22 +0100 3307931 http://www.medworm.com/index.php?rid=3307930&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F213%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3307930 Thu, 25 Feb 2010 23:28:22 +0100 3307930 http://www.medworm.com/index.php?rid=3307929&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F205%3Frss%3D1 Antigen binding to the B-cell antigen receptor (BCR) leads to receptor triggering and B-lymphocyte activation. Here, we have probed the molecular requirements for BCR triggering in primary murine B cells using a set of defined soluble haptenated peptides. Bi- and trivalent haptens activated the BCR, as measured by protein phosphorylation, Ca2+ influx, BCR down-modulation and CD69, CD86 and MHC class II up-regulation. In contrast, four distinct monovalent haptens were ineffective. Next, we used two different anti-idiotypic antibodies, which bind to the antigen-combining site of the BCR. Again, monovalent Fab fragments were ineffective, whereas bivalent antibodies could stimulate the BCR. These findings are compatible with ligand-induced clustering of monomeric BCRs or re-organization of BCR... International Immunology journals http://www.medworm.com/rss/comments.php?id=3307929 Thu, 25 Feb 2010 23:28:22 +0100 3307929 http://www.medworm.com/index.php?rid=3307928&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F191%3Frss%3D1 Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of insulin-producing pancreatic β cells. In both humans and the non-obese diabetic (NOD) mouse model of T1D, class II MHC alleles are the primary determinant of disease susceptibility. However, class I MHC genes also influence risk. These findings are consistent with the requirement for both CD4+ and CD8+ T cells in the pathogenesis of T1D. Although a large body of work has permitted the identification of multiple mechanisms to explain the diabetes-protective effect of particular class II MHC alleles, studies examining the protective influence of class I alleles are lacking. Here, we explored this question by performing biochemical and structural analyses of the murine class I MHC molecule H-2K... International Immunology journals http://www.medworm.com/rss/comments.php?id=3307928 Thu, 25 Feb 2010 23:28:22 +0100 3307928 http://www.medworm.com/index.php?rid=3307927&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F179%3Frss%3D1 In this study we found that, at the early stage of infection, depletion of CD25+ cells reduced both bacterial load and granuloma formation in mice infected with Mycobacterium tuberculosis strains, such as M. tuberculosis Erdman or M. tuberculosis Kurono. However, at a later stage of infection, bacterial burden and histopathology were similar regardless of depletion of CD25+ cells. Severe combined immunodeficient (SCID) mice reconstituted with CD4+CD25– T cells alone or a combination of CD4+CD25+ and CD4+CD25– T cells showed similar bacterial loads and survival kinetics after infection with M. tuberculosis Erdman. Consistent with in vivo data, in vitro studies revealed that mycobacterial antigens, purified protein derivative of tuberculin (PPD), failed to induce the suppressive ... International Immunology journals http://www.medworm.com/rss/comments.php?id=3307927 Thu, 25 Feb 2010 23:28:22 +0100 3307927 http://www.medworm.com/index.php?rid=3307926&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F167%3Frss%3D1 In conclusion, the modulation of glycosyltransferases MGAT3 and MGAT5 by synthetic GN4C correlated with the improvement of NK cell effector functions and the augmentation of tumor cells sensitivity to NK cell-mediated cytotoxicity. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3307926 Thu, 25 Feb 2010 23:28:22 +0100 3307926 http://www.medworm.com/index.php?rid=3307925&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F157%3Frss%3D1 Hyper-coagulation, hypothermia, systemic inflammatory responses and shock are major clinical manifestations of endotoxin shock syndrome in human. As previously reported, mice primed with heat-killed Propionibacterium acnes are highly susceptible to the action of LPS to induce tumour necrosis factor (TNF)- and to that of TNF- to trigger lethal shock. Here we investigated the mechanisms underlying the P. acnes-induced sensitization to LPS and TNF- and the development of individual symptoms after subsequent challenge with LPS or TNF-. Propionibacterium acnes-primed wild-type (WT) mice, but not naive mice, exhibited hyper-coagulation with elevated levels of thrombin–antithrombin complexes and anti-fibrinolytic plasminogen activator inhibitor 1 in their plasma, hypothermia, systemic infla... International Immunology journals http://www.medworm.com/rss/comments.php?id=3307925 Thu, 25 Feb 2010 23:28:22 +0100 3307925 http://www.medworm.com/index.php?rid=3307924&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F149%3Frss%3D1 Fc receptors specifically bind to the Fc region of Igs to mediate the unique functions to each class of Igs. To identify a novel Fc receptor for IgM, we searched expressed sequence tag database for molecules containing Ig domains with homology to those of known Fc receptors for IgM, Fc/µR and polymeric Ig receptor. As a result, we identified TOSO/Fas apoptotic inhibitory molecule 3 (FAIM3) as a possible Fc receptor for IgM. HeLa cells transfected with a TOSO/FAIM3-expression vector bound to IgM but not IgG and were able to internalize IgM-conjugated beads but not IgG-conjugated beads, suggesting that TOSO/FAIM3 is indeed a receptor for IgM (FcµR). FcµR protein was expressed predominantly on B-lineage cells; expression of the Fcmr transcripts was observed from the pre-B-ce... International Immunology journals http://www.medworm.com/rss/comments.php?id=3307924 Thu, 25 Feb 2010 23:28:22 +0100 3307924 http://www.medworm.com/index.php?rid=3307923&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F143%3Frss%3D1 Despite lacking the adaptive immunity that is found in higher vertebrates, insects are able to defend themselves from a large battery of pathogens by multiple innate immune responses using molecular mechanisms that are strikingly similar to the innate immune responses of other multicellular organisms, including humans. The fruit fly Drosophila melanogaster is therefore an excellent model organism for studying the basic principles of innate immunity using genetic and molecular biology techniques. In Drosophila, invading pathogens that pass through the epithelial barriers (a first line of self-defense) can encounter humoral and cellular responses that utilize pattern-recognition receptors to identify pathogen-associated molecular patterns in the hemolymph or on the immune cell surface. Some ... International Immunology journals http://www.medworm.com/rss/comments.php?id=3307923 Thu, 25 Feb 2010 23:28:22 +0100 3307923 http://www.medworm.com/index.php?rid=3307922&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2F141%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3307922 Thu, 25 Feb 2010 23:28:22 +0100 3307922 http://www.medworm.com/index.php?rid=3307921&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F3%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3307921 Thu, 25 Feb 2010 23:28:22 +0100 3307921 http://www.medworm.com/index.php?rid=3288947&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F2%2F129%3Frss%3D1 Although recent studies have identified regulatory roles for Foxp3+CD8+ T cells, the mechanisms that induce their development and underlie their functions in vivo have not been elucidated. Here, we show that IL-6 positively regulates the Foxp3+CD8+ T-cell development and function. The Foxp3+CD8+ T cells that differentiated in vitro in the presence of IL-6 suppressed autoimmune colitis and arthritis in vivo. Moreover, Foxp3+CD8+ T cells that developed in vivo in the presence of enhanced IL-6 signaling suppressed the development of a spontaneous Th17 cell-mediated autoimmune arthritis. Thus, we concluded that Foxp3+CD8+ T cells develop in response to IL-6 and regulate chronic inflammation in Th17 cell-mediated F759 autoimmune arthritis. These results suggested that Foxp3+CD8+ T cells may dev... International Immunology journals http://www.medworm.com/rss/comments.php?id=3288947 Fri, 19 Feb 2010 17:25:26 +0100 3288947 http://www.medworm.com/index.php?rid=3288946&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F2%2F113%3Frss%3D1 We examined the effects of FcRI–chemokine receptor (CCR) 1 co-stimulation on receptor localization and cellular morphology of bone marrow-derived mast cells. Whereas FcRI and CCR1 co-localized at the plasma membrane in unsensitized cells, sensitization with IgE promoted internalization of CCR1 molecules. Co-stimulation of FcRI and CCR1 with antigen and macrophage inflammatory protein-1 was more effective than FcRI stimulation alone in causing leading edge formation, flattened morphology, membrane ruffles and ganglioside (GM1+) lipid mediator release. Co-stimulation resulted in phalloidin-positive cytoneme-like cellular extensions, also known as tunneling nanotubes, which originated at points of calcium accumulation. This is the first report of cytoneme formation by mast cells. To det... International Immunology journals http://www.medworm.com/rss/comments.php?id=3288946 Fri, 19 Feb 2010 17:25:26 +0100 3288946 http://www.medworm.com/index.php?rid=3288945&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F2%2F101%3Frss%3D1 Clonal anergy has been well recognized as an important mechanism of B cell immunologic tolerance. However, the properties of anergic B cells and especially their role in the development of autoimmune disease in susceptible animals have been controversial. Here we show that low-affinity anti-DNA anergic B cells populate the mature B-cell compartment in the mouse spleen in excessive numbers and display paradoxical behavior in response to a combined B-cell receptor/TLR9 activation. Surprisingly, B-cell anergy was maintained in aged NZB/NZW F1 mice that develop a systemic lupus erythematosus (SLE)-like autoimmune disease. In several parameters of anergy, such as calcium mobilization and antibody secretion, the lupus-prone mice appeared more anergic than their non-autoimmune counterparts. We co... International Immunology journals http://www.medworm.com/rss/comments.php?id=3288945 Fri, 19 Feb 2010 17:25:26 +0100 3288945 http://www.medworm.com/index.php?rid=3288944&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F2%2F91%3Frss%3D1 In this study, we show that anti-GPR56 mAbs, among leukocytes, prevalently recognize NK cells. In particular, these mAbs brightly stain CD56dull CD16+ NK cells while react poorly with CD56bright CD16+/– NK cells. Consistently, we found that GPR56 was expressed on NK cells populating inflamed peripheral tissues while it was absent in lymph node-derived NK cells. We also show that activating stimuli, such as cytokines or exposure to monocyte-derived dendritic cell, down-regulate NK cell expression of GPR56 both at the protein and at the transcriptional level. Interestingly, IL-18, known to induce de novo expression of CCR7 on CD56dull CD16+ NK cells, displayed the highest capability of modulating GPR56. Thus, together with the identification of GPR56 as a novel marker capable of discri... International Immunology journals http://www.medworm.com/rss/comments.php?id=3288944 Fri, 19 Feb 2010 17:25:25 +0100 3288944 http://www.medworm.com/index.php?rid=3288943&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F2%2F81%3Frss%3D1 IL-23 is a key cytokine in promotion of chronic inflammation. Here, we address if its pro-inflammatory potential can be harnessed to protect against chronic cryptococcosis. Mice were infected with Cryptococcus neoformans and treated with recombinant IL-23. Administration of IL-23 led to prolonged survival and reduced fungal burden but was inferior to IL-12 treatment. Independent of endogenous IL-23/IL-12, IL-23 treatment induced an altered cytokine profile accompanied by marked changes in composition of the inflammatory infiltrate characterized by T cell and dendritic cell recruitment. Although IL-23 induced hallmarks of the Th17 pathway, also non-T cells produced IL-17A and IL-22. IL-23 treatment of T-cell-deficient mice resulted in increased IL-17A and IL-22 production and modulation of ... International Immunology journals http://www.medworm.com/rss/comments.php?id=3288943 Fri, 19 Feb 2010 17:25:25 +0100 3288943 http://www.medworm.com/index.php?rid=3288942&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F2%2F71%3Frss%3D1 In this study, we investigated the in vivo role of FcRs on the modulation of humoral immune response. In order to get well-defined immune complexes that can bind to both the activating and the inhibitory FcRs, we designed a mono-biotinylated single-chain fragment variable construct from the rat anti-mouse CD16/32 clone 2.4G2, linked to avidin–FITC, and tested its effect on the FITC–hapten-specific T-independent type 2 (TI-2) and T-dependent (TD) immune response. When injected intravenously in mice, the complex bound to a small portion of B220+, CD11bhigh and CD11chigh cells and was localized in the spleen on marginal zone macrophages 15 min after treatment. When applied as a booster following primary immunization with TI-2 (FITC–dextran) or TD (FITC–keyhole limpet h... International Immunology journals http://www.medworm.com/rss/comments.php?id=3288942 Fri, 19 Feb 2010 17:25:25 +0100 3288942 http://www.medworm.com/index.php?rid=3288941&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F2%2F65%3Frss%3D1 This article describes and compares these models and outlines recent evidence supporting the myeloid-based model. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3288941 Fri, 19 Feb 2010 17:25:25 +0100 3288941 http://www.medworm.com/index.php?rid=3288940&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F2%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3288940 Fri, 19 Feb 2010 17:25:25 +0100 3288940 http://www.medworm.com/index.php?rid=3097446&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F1%2F53%3Frss%3D1 In this study, we have shown the role of IL-13 in the regulation of Th1 immunity in both normal healthy and DL-bearing host. IL-13 pre-treatment inhibits the induction of 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity and delayed-type hypersensitivity (DTH) in antigen-challenged mice, which have been confirmed by neutralizing IL-13 by systemic delivery of non-signaling decoy receptor IL-13R2. Furthermore, IL-13 neutralization enhances the splenocyte proliferation, which has been inhibited by IL-13 administration. Adoptive transfer of splenocyte from IL-13-pre-treated mice and macrophages incubated with IL-13 and pulsed with antigens suppresses the DTH as well in antigen-challenged recipient mice. In addition, it also suppresses the production of pro-inflammatory cytokine and ... International Immunology journals http://www.medworm.com/rss/comments.php?id=3097446 Thu, 17 Dec 2009 14:34:26 +0100 3097446 http://www.medworm.com/index.php?rid=3097445&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F1%2F45%3Frss%3D1 Anti-glomerular basement membrane antibody disease (anti-GBM disease) is a rare disorder characteristic of universally poor outcome. Fc receptors (FcRs) play important roles in anti-GBM disease based on evidence from animal models. Copy number variation (CNV) influences disease susceptibility. The FcRs genes show CNV, and CNV of the FCGR3B gene is associated with glomerulonephritis in systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated small vasculitis. Here, we investigated CNV of three FCGR genes, including two (FCGR3A and FCGR3B) for activating FcRs and one (FCGR2B) for inhibitory FcR by duplex quantitative real-time PCR. Copy numbers were analyzed by Applied Biosystems CopyCaller Software v1.0. We first demonstrated the distribution of CNV of FCGR3A, FCGR3B... International Immunology journals http://www.medworm.com/rss/comments.php?id=3097445 Thu, 17 Dec 2009 14:34:26 +0100 3097445 http://www.medworm.com/index.php?rid=3097444&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F1%2F35%3Frss%3D1 Leucocyte function-associated antigen-1 (LFA-1) is known to be involved in immune reactions leading to allograft rejection. The role of deactivating LFA-1 in this context has not been investigated yet, although it is accepted that regulating LFA-1 activity is essential for T-cell function. Expressing LFA-1 locked in an active state in mice (LFA-1d/d) allowed us to investigate the in vivo function of LFA-1 deactivation for allograft rejection in a model of heterotopic cardiac transplantation. We provide in vivo evidence that regulating LFA-1 activity from an active to an inactive state controls antigen-specific priming and proliferation of T cells in response to allogeneic stimuli. Consequently, defective LFA-1 deactivation significantly prolonged cardiac allograft survival. Furthermore, re... International Immunology journals http://www.medworm.com/rss/comments.php?id=3097444 Thu, 17 Dec 2009 14:34:26 +0100 3097444 http://www.medworm.com/index.php?rid=3097443&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F1%2F25%3Frss%3D1 Melatonin is a hormone that has immunomodulatory activity and is believed to influence the production of antibodies in mammals. The aim of the present study was to investigate the effect of suppressed melatonin synthesis on the antibody production. BALB/c mice were immunized with T-cell-dependent (TD) and T-cell-independent (TI) antigens and kept under (i) normal lighting, (ii) constant exposure to light, (iii) exposed to light and treated daily with melatonin. It was revealed that melatonin modulated TD and TI antibody production. Suppressed melatonin synthesis increased the amount of IgM, IgG1, IgG2b and IgG3 antibodies after immunization with TI antigen. The level of TD antibodies IgM, IgG2a, IgG2b and IgG3 also increased, however, the antigen-specific antibodies of IgG1 isotype signifi... International Immunology journals http://www.medworm.com/rss/comments.php?id=3097443 Thu, 17 Dec 2009 14:34:25 +0100 3097443 http://www.medworm.com/index.php?rid=3097442&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F1%2F13%3Frss%3D1 Chronic viral infections are often characterized by CD8 T-cell responses with poor cytokine secretion potential and limited expansion of the CD8 T-cell pool, collectively referred to as CD8 T-cell exhaustion. Exhaustion of lymphocytic choriomeningitis virus (LCMV)-specific CD8 T cells was shown to be partially regulated by the inhibitory receptor programmed death 1 (PD-1). Here, we demonstrate that exhausted LCMV-specific CD8 T cells also express the negative regulatory receptor lymphocyte activation gene 3 (LAG-3) which is mainly expressed on cells co-expressing the negative regulatory receptors PD-1 and Tim-3. Expression levels of LAG-3 on anti-viral CD8 T cells remain stable over short-term in vitro stimulations in presence of antigenic peptide. Nevertheless, in vitro and in vivo blocka... International Immunology journals http://www.medworm.com/rss/comments.php?id=3097442 Thu, 17 Dec 2009 14:34:25 +0100 3097442 http://www.medworm.com/index.php?rid=3097441&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F1%2F7%3Frss%3D1 Upon encounter with antigen, CD4+ T cells differentiate into effector Th subsets with distinctive functions that are related to their unique cytokine profiles and anatomical locations. One of the most important Th functions is to provide signals to developing B cells that induce specific and appropriate antibody responses. The major CD4+ T cell subset that helps B cells is the T follicular helper (TFH) cell, whose expression of the chemokine receptor CXCR5 [chemokine (C–X–C motif) receptor 5] serves to localize this cell to developing germinal centers (GCs) where it provides instructive signals leading to Ig class switching and somatic mutation. TFH cells produce high levels of IL-21, a cytokine that is critical for GC formation and also for the generation of TFH cells. Althoug... International Immunology journals http://www.medworm.com/rss/comments.php?id=3097441 Thu, 17 Dec 2009 14:34:25 +0100 3097441 http://www.medworm.com/index.php?rid=3097440&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F1%2F1%3Frss%3D1 Invariant NKT (iNKT) cells bridge innate and acquired immunity and play an important role in both protective and regulatory responses. The nature of the response is dictated by the initial cytokine environment: interaction with IL-10-producing cells induces negative regulatory Th2/regulatory T cell-type iNKT cells, while that with IL-12-producing cells results in pro-inflammatory Th1-type responses. Particularly, in the anti-tumor response, iNKT cells mediate adjuvant activity by their production of IFN-, which in turn activates both innate and acquired immune systems. Thus, upon activation of iNKT cells, both MHC– and MHC+ tumor cells can be efficiently eliminated. On the basis of these mechanisms, iNKT cell-targeted adjuvant cell therapies have been developed and have shown great p... International Immunology journals http://www.medworm.com/rss/comments.php?id=3097440 Thu, 17 Dec 2009 14:34:25 +0100 3097440 http://www.medworm.com/index.php?rid=3097439&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F22%2F1%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3097439 Thu, 17 Dec 2009 14:34:25 +0100 3097439 http://www.medworm.com/index.php?rid=3005107&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F12%2F1351%3Frss%3D1 Sustained extracellular signal-regulated kinase (ERK)-signaling plays a critical role in T-cell-mediated IL-2 production. Although many downstream targets are known for ERK, details remain unknown about which molecules play functional roles in IL-2 production. Here, we addressed this question using proteomic analysis of nuclear proteins from TCR-activated T cells and identified hnRNP-K as one of the ERK targets essential for IL-2 production. hnRNP-K was previously shown by others to be a direct substrate of ERK and form complexes with multiple signaling proteins as well as DNA and RNA. Our data showed a clear ERK-dependent increase in one form of hnRNP-K after TCR stimulation. Small interfering RNA-mediated gene knockdown of hnRNP-K expression abrogated IL-2 production by T cells. Moreover... International Immunology journals http://www.medworm.com/rss/comments.php?id=3005107 Wed, 18 Nov 2009 23:15:03 +0100 3005107 http://www.medworm.com/index.php?rid=3005106&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F12%2F1341%3Frss%3D1 The release of the soluble form of tumor necrosis factor (TNF)-alpha from the plasma membrane occurs through the activation of the secretase tumor necrosis factor-alpha-converting enzyme (TACE). The current study was designed to examine whether the anti-Ro/SSA autoantibodies (Abs) are capable to regulate TACE expression in non-neoplastic human salivary gland epithelial cells (SGEC) cultures. We investigated the effect of anti-Ro/SSA Abs on the localization and abundance of cell-surface TACE and on TACE pro-domain-shedding and activation. In addition, the potential physiological consequences of TNF-alpha blockage by the biological agent Adalimumab on post-translational regulation of TACE are discussed. Anti-Ro/SSA Abs were purified from IgG fractions of patients with primary Sjögren's ... International Immunology journals http://www.medworm.com/rss/comments.php?id=3005106 Wed, 18 Nov 2009 23:15:03 +0100 3005106 http://www.medworm.com/index.php?rid=3005105&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F12%2F1329%3Frss%3D1 MBP-specific autoreactive T cells are considered pro-inflammatory T cells and thought to play an important role in the pathogenesis of multiple sclerosis (MS). Here, we report that MBP83–99-specific T cells generated from MS patients (n = 7) were comprised of pro-inflammatory and regulatory subsets of distinct phenotypes. The pro-inflammatory phenotype was characterized by high production of IFN-, IL-6, IL-21 and IL-17 and low expression of FOXP3, whereas the regulatory subset expressed high levels of FOXP3 and exhibited potent regulatory functions. The regulatory subset of MBP-specific T cells appeared to expand from the CD4+CD25– T-cell pool. Their FOXP3 expression was stable, independent of the activation state and it correlated with suppressive function and inversely with t... International Immunology journals http://www.medworm.com/rss/comments.php?id=3005105 Wed, 18 Nov 2009 23:15:03 +0100 3005105 http://www.medworm.com/index.php?rid=3005104&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F12%2F1317%3Frss%3D1 TCR expression on double-positive (DP) thymocytes is a prerequisite for thymic selection that results in the generation of mature CD4+ and CD8+ single-positive T cells. TCR is expressed at very low level on preselection DP thymocytes and is dramatically up-regulated on positively selected thymocytes. However, mechanism governing TCR expression on developing thymocytes is not understood. In the present report, we demonstrate that the intra-cytoplasmic (IC) domain of CD3 plays a critical role in regulating TCR expression on DP thymocytes. We provide genetic and biochemical evidence to show that the CD3 IC domain mutations result in elevated expression of fully assembled TCR on DP thymocytes. We also demonstrate that TCR up-regulation on DP thymocytes in these transgenic mice occurs in a liga... International Immunology journals http://www.medworm.com/rss/comments.php?id=3005104 Wed, 18 Nov 2009 23:15:03 +0100 3005104 http://www.medworm.com/index.php?rid=3005103&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F12%2F1311%3Frss%3D1 This article is aimed at introducing such individual work and how these areas have contributed to our understanding of the mechanisms of allergic reactions. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3005103 Wed, 18 Nov 2009 23:15:03 +0100 3005103 http://www.medworm.com/index.php?rid=3005102&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F12%2F1303%3Frss%3D1 IL-5 was originally defined as a T-cell-derived cytokine that triggers activated B cells for terminal differentiation into antibody-secreting plasma cells, at least in mice. Concurrently, IL-5 was recognized as the major maturation and differentiation factor for eosinophils in mice and humans. Over-expression of IL-5 significantly increases eosinophil numbers and antibody levels in vivo. Conversely, mice lacking a functional gene for IL-5 or the IL-5 receptor alpha chain (IL-5R) display a number of developmental and functional impairments in B-cell and eosinophil lineages. In addition to the Janus kinase–signal transducer and activator of transcription pathway, the tyrosine kinases Lyn and Btk (Bruton agammaglobulinemia tyrosine kinase) are involved, and Ras GTPase–extracellula... International Immunology journals http://www.medworm.com/rss/comments.php?id=3005102 Wed, 18 Nov 2009 23:15:03 +0100 3005102 http://www.medworm.com/index.php?rid=3005101&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F12%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=3005101 Wed, 18 Nov 2009 23:15:03 +0100 3005101 http://www.medworm.com/index.php?rid=2928143&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1301%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2928143 Mon, 26 Oct 2009 13:19:26 +0100 2928143 http://www.medworm.com/index.php?rid=2928142&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1291%3Frss%3D1 IFN- signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN- signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN- receptor-deficient (IFN-R–/–) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN- is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the Th1/Th17 balance between IFN-R–/– NOD and wild-type NOD mice. There is also no diffe... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928142 Mon, 26 Oct 2009 13:19:26 +0100 2928142 http://www.medworm.com/index.php?rid=2928141&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1277%3Frss%3D1 We report that naive CD4 T cells from aged mice (ANCD4 cells) showed greater apoptosis upon primary activation than those from young (Yg) mice, with loss of mitochondrial membrane potential, poor activation of Rel family transcription factors and increased DNA damage. Their ability to enhance glycolysis, produce lactate and induce autophagy following activation was also compromised. ANCD4 cells remained susceptible to death beyond first cell division. Activated ANCD4 cells also showed poor transition to a ‘central memory’ (CM) CD44high, CD62Lhigh phenotype in vitro. This correlated with low proportions of CM cells in Ad mice in vivo. Functionally, too, IFN-gamma responses recalled from T cells of immunized Ad mice, poor to begin with, worsened with time as compared with Yg mice... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928141 Mon, 26 Oct 2009 13:19:26 +0100 2928141 http://www.medworm.com/index.php?rid=2928140&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1269%3Frss%3D1 Glucocorticoid receptor (GR) signaling plays an important role in the selection and apoptosis of thymocytes. Besides nuclear translocation, mitochondrial translocation of the ligand-bound GR in lymphoid cells was also shown, which might determine glucocorticoid (GC)-induced apoptosis sensitivity. In the present work, we followed the ligand-induced GR trafficking in CD4+CD8+ double-positive (DP) thymocytes. Using confocal microscopy, we found that upon short-term in vitro GC analog [dexamethasone (DX)] treatment, the GR translocates into the mitochondria but not into the nucleus in DP cells. We also analyzed the GR redistribution in cytosolic, nuclear and mitochondrial fractions of unseparated thymocytes by western blot and confirmed that in DX-treated cells a significant fraction of the GR... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928140 Mon, 26 Oct 2009 13:19:26 +0100 2928140 http://www.medworm.com/index.php?rid=2928139&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1263%3Frss%3D1 Serum transfer from arthritic K/BxN mice into naive animals results in arthritis. Mast cells have been shown to be essential since mice lacking these cell type do not develop arthritis upon serum injection. Mast cell function depends on the release of granules filled with mediators such as histamine. Mice deficient in histidine decarboxylase (HDC–/–) that do not produce histamine and mice deficient for histamine receptor 1 (H1R–/–) or histamine receptor 2 (H2R–/–) were injected with arthritogenic sera from the K/BxN mice, and the progression of arthritis was observed through the next 2 weeks. HDC–/– mice that are histamine free developed a milder form of arthritis in comparison with the wild-type controls. In both receptor-deficient mice as w... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928139 Mon, 26 Oct 2009 13:19:26 +0100 2928139 http://www.medworm.com/index.php?rid=2928138&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1251%3Frss%3D1 Influenza affects most of the world's population annually, often causing a secondary infection, but pathological mechanisms of influenza virus infection remain unclear. We have found that influenza viruses have a selective preference for infecting monocytes and mature immune effector cells. This paper provides evidence that influenza virus infection increases the expression of granzyme B (GrB) in monocytes, activated T and B cells. All GrB+ cells had cytolytic function. GrB+CD62Lhigh central memory (TCM) cells were fast response population to virus infection when compared with GrB+CD62Llow population. The influenza virus-infected PBMC could be killed by GrB+ cells. We propose the following mechanism for influenza: (i) influenza virus within the respiratory tract overcomes humoral defenses;... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928138 Mon, 26 Oct 2009 13:19:26 +0100 2928138 http://www.medworm.com/index.php?rid=2928137&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1239%3Frss%3D1 Yersinia species during infection adhere to host immune cells primarily to macrophages and employ its secretary proteins known as Yersinia outer proteins to trigger death in infected cells. In the present study, it is shown that recombinant Yersinia outer protein J (rYopJ) could induce apoptosis in murine peritoneal macrophages in vitro as assessed by morphological features, internucleosomal DNA fragmentation, change in mitochondrial membrane potential (MMP) (m), activation of caspases and Annexin V binding. rYopJ-induced cell death was dose and time dependent. Pre-treatment with broad-spectrum caspase inhibitor Z-VAD-FMK, caspase-3 inhibitor Ac-DEVD-CHO and caspase-8 inhibitor Z-IETD-FMK prevented the change in MMP and DNA fragmentation, suggesting caspase-dependent apoptosis of rYopJ-tre... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928137 Mon, 26 Oct 2009 13:19:26 +0100 2928137 http://www.medworm.com/index.php?rid=2928136&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1225%3Frss%3D1 CD81 is a component of the CD19/CD21 co-receptor complex in B cells. However, the role of CD81 in B cell activation has not been clearly elucidated. Here, we demonstrate that Cd81–/– B cells stimulated via their B cell receptor fluxed higher intracellular-free calcium ion along with increased phosphorylation of spleen tyrosine kinase and phospholipase gamma 2. Additionally, Cd81–/– B cells responded to toll like receptor 4 stimulation with increased nuclear factor-kappa B activation, cell proliferation and antibody secretion compared with wild-type B cells. Cd81–/– mice also mounted a significantly higher immune response to T-independent antigens than their wild-type counterparts. Finally, analysis of Cd81–/– B cells that were generated by bo... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928136 Mon, 26 Oct 2009 13:19:26 +0100 2928136 http://www.medworm.com/index.php?rid=2928135&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1213%3Frss%3D1 We address here the role of CD4 T cell cooperation in the activation of CD4 T cells. Administration of aggregated hen egg lysozyme (HEL) without microbial adjuvant to BALB/c mice normally generates cytokine-producing CD4 T cells specific for the HEL major peptide, HEL105–120, as well as CD4 T cells specific for HEL non-major peptides. The prior administration of HEL105–120 ablates the generation of cytokine-secreting CD4 T cells specific for HEL105–120, as well as the CD4 T cells specific for HEL non-major peptides, normally generated upon HEL challenge. Thus, the activation of HEL non-major peptide-specific CD4 T cells appears to depend upon the HEL105–120-specific CD4 T cell population. In contrast, when HEL105–120 and saline-treated mice are challenged with... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928135 Mon, 26 Oct 2009 13:19:26 +0100 2928135 http://www.medworm.com/index.php?rid=2928134&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1205%3Frss%3D1 Mutations in genes involved in macroautophagy have been found to be associated with Morbus Crohn, also called Crohn's disease (CD), an inflammatory bowel disease. Taking this disease as an example for pathogenesis due to altered macroautophagy, we discuss here how macroautophagy supports innate and adaptive immunity. This support ranges from maintenance of components of the immune system, antigen processing for presentation to the immune system, to education of the immune system in order to distinguish self from dangerous non-self. A better understanding of these mechanisms should allow us not only to develop therapeutical strategies for CD but also to utilize macroautophagy for enhanced immunity against pathogens and tumors. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2928134 Mon, 26 Oct 2009 13:19:26 +0100 2928134 http://www.medworm.com/index.php?rid=2928133&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2F1199%3Frss%3D1 Autophagy is a catabolic process by which cells degrade their own cytoplasmic constituents. Cells respond to the stress response of nutrient deficiency by degrading a portion of their cellular components to produce amino acids and energy. Recently, it became evident that the autophagic machinery is also involved in a kind of innate immune system. Some bacteria that invade mammalian cells are eventually entrapped in an autophagic membrane structure. In this review, we describe the current understanding of three of the basic components of the canonical autophagy machinery—LC3, the Atg16L complex and phosphatidylinositol 3-phosphate (PI3P)—which are dynamically associated with the autophagic structure. LC3 is proposed to function in autophagosome closure, whereas the Atg16L comple... International Immunology journals http://www.medworm.com/rss/comments.php?id=2928133 Mon, 26 Oct 2009 13:19:26 +0100 2928133 http://www.medworm.com/index.php?rid=2928132&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F11%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2928132 Mon, 26 Oct 2009 13:19:26 +0100 2928132 http://www.medworm.com/index.php?rid=2825567&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1185%3Frss%3D1 In this study, the potential of lactoferrin to modulate surface expression of MHC II, CD80, CD86 and CD40 from bone marrow-derived dendritic cells (BMDCs) was examined. Generally, lactoferrin decreased pro-inflammatory cytokines [tumor necrosis factor (TNF)-, IL-6 and IL-12p40] and chemokines [macrophage inflammatory protein (MIP)-1 and MIP-2] and increased regulatory cytokine, transforming growth factor-β1 and a T-cell chemotatic factor, monocyte chemotactic protein-1, from uninfected or BCG-infected BMDCs. Culturing BCG-infected BMDCs with lactoferrin also enhanced their ability to respond to IFN- activation through up-regulation of maturation markers: MHC I, MHC II and the ratio of CD86:CD80 surface expression. Furthermore, lactoferrin-exposed BCG-infected DCs increased stimulation... International Immunology journals http://www.medworm.com/rss/comments.php?id=2825567 Wed, 23 Sep 2009 23:00:00 +0100 2825567 http://www.medworm.com/index.php?rid=2825566&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1175%3Frss%3D1 This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2825566 Wed, 23 Sep 2009 23:00:00 +0100 2825566 http://www.medworm.com/index.php?rid=2825565&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1163%3Frss%3D1 Pharmacological inhibitors that block amyloid precursor protein (APP) cleavage and the formation of senile plaques are under development for the treatment of familial Alzheimer's disease. Unfortunately, many inhibitors that block -secretase-mediated cleavage of APP also have immunosuppressive side effects. In addition to APP, numerous other proteins undergo -secretase-mediated cleavage. In order to develop safer inhibitors, it is necessary to determine which of the -secretase substrates contribute to the immunosuppressive effects. Because APP family members are widely expressed and are reported to influence calcium flux, transcription and apoptosis, they could be important for normal lymphocyte maturation. We find that APP and amyloid precursor-like protein 2 are expressed by stromal cells... International Immunology journals http://www.medworm.com/rss/comments.php?id=2825565 Wed, 23 Sep 2009 23:00:00 +0100 2825565 http://www.medworm.com/index.php?rid=2825564&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1151%3Frss%3D1 Activated mature T cells induce various inhibitory receptors implicated in maintaining peripheral tolerance in response to the trans-acting ligands. Interestingly, paired Ig-like receptor (PIR)-B, an inhibitory MHC class I receptor on B cells and myeloid cells, could be involved in regulating early T cell development because epitope for PIR is detected on pre-thymic T/NK progenitors but not on thymocytes or mature T cells. We hypothesized that PIR-B is not only a regulator for T cell development but is also detrimental if expressed on mature T cells. Here we demonstrated, using PIR-B-deficient fetuses, that PIR-B is indeed expressed on the T cell progenitors but failed to identify its distinctive roles in the development. Forced expression of PIR-B in thymocytes and mature T cells also res... International Immunology journals http://www.medworm.com/rss/comments.php?id=2825564 Wed, 23 Sep 2009 23:00:00 +0100 2825564 http://www.medworm.com/index.php?rid=2825563&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1145%3Frss%3D1 Fluorescent protein that detects caspase-3 activation was used for the time-lapse observation of CTL–target cell interaction. In the target cells transfected with SCAT3.1 (caspase-3-sensitive fusion protein) complementary DNA, caspase-3 activation can be detected significantly earlier than the commonly used annexin-V binding that detects membrane change in apoptotic cells. Moreover, during the cytolytic interaction between OE4 CTL and W3 tumor target cells, detachment of CTL from the target cells occurred prior to caspase-3 activation and death of the target cells, indicating very early sensing of apoptotic target cells by CTL. This early detachment of OE4 CTL from W3 target cells was inhibited by the expression of CD80 co-stimulatory molecule on the target cells. Taken together, tim... International Immunology journals http://www.medworm.com/rss/comments.php?id=2825563 Wed, 23 Sep 2009 23:00:00 +0100 2825563 http://www.medworm.com/index.php?rid=2825562&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1135%3Frss%3D1 Dendritic cells (DCs) are responsible for the initiation of immune responses. Our study demonstrates a new pathway for generating a large quantity of stimulatory monocyte-derived DCs (Mo-DCs) from human monocytes using anti-4-1BB ligand (4-1BBL) mAb to trigger reverse signaling. The anti-4-1BBL-driven Mo-DCs (DCs-4-1BBL) not only express higher levels of CD86, CD83 and HLA-DR, when compared with the Mo-DCs matured by tumor necrosis factor , but also exhibit a unique phenotype that expresses lower levels of PD-L1. High levels of GM-CSF, M-CSF and Flt3 ligand (FL) were found in the anti-4-1BBL-differentiation culture. Neutralizing M-CSF, GM-CSF and FL inhibited Mo-DC proliferation stimulated by anti-4-1BBL mAb, suggesting that M-CSF, GM-CSF and FL are involved in cell proliferation stimulate... International Immunology journals http://www.medworm.com/rss/comments.php?id=2825562 Wed, 23 Sep 2009 23:00:00 +0100 2825562 http://www.medworm.com/index.php?rid=2825561&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1125%3Frss%3D1 Mannan-binding lectin (MBL) is a C-type serum lectin, which is believed to play an important role in the innate immunity against a variety of pathogens. MBL can bind to sugar determinants of a wide variety of microorganisms, neutralize them and inhibit infection by complement activation through the lectin pathway and opsonization by collectin receptors. Given that small intestine is a predominant site of extrahepatic expression of MBL, here we addressed the question whether MBL is involved in mucosal innate immunity. The carbohydrate recognition domain (CRD) genes of mouse MBL-C (mMBL-C) were cloned and expressed in Escherichia coli. Recombinant mMBL-C-CRD binds to Shigella flexneri 2a in a calcium-dependent manner and that interaction could be blocked by the anti-mMBL-C-CRD antibody. mMBL... International Immunology journals http://www.medworm.com/rss/comments.php?id=2825561 Wed, 23 Sep 2009 23:00:00 +0100 2825561 http://www.medworm.com/index.php?rid=2825560&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1113%3Frss%3D1 T cell development in the thymus is controlled by thymic epithelial cells (TE). While it is accepted that TE interact with maturing T cells, the mechanisms by which they trigger ‘death by neglect’ of double-positive (DP) thymocytes are poorly understood. We and others have demonstrated a role for TE-derived glucocorticoids (GCs) in this process. We have studied TE-induced apoptosis using an in vitro system based on co-culturing a thymic epithelial cell line (TEC) with DP thymic lymphoma cells or thymocytes (DP thymic cells). Here, we demonstrate that nitric oxide (NO·) is also involved in this death process. The inducible nitric oxide synthase (iNOS) inhibitors NG-methyl-L-arginine and 1,4-PBIT attenuated TEC-induced apoptosis of DP thymic cells. Co-cultivation of TEC wi... International Immunology journals http://www.medworm.com/rss/comments.php?id=2825560 Wed, 23 Sep 2009 23:00:00 +0100 2825560 http://www.medworm.com/index.php?rid=2825559&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1105%3Frss%3D1 Regulatory T cells (Tregs), either natural or induced, suppress a variety of physiological and pathological immune responses. One of the key issues for understanding Treg function is to determine how they suppress other lymphocytes at the molecular level in vivo and in vitro. Here we propose that there may be a key suppressive mechanism that is shared by every forkhead box p3 (Foxp3)+ Treg in vivo and in vitro in mice and humans. When this central mechanism is abrogated, it causes a breach in self-tolerance and immune homeostasis. Other suppressive mechanisms may synergistically operate with this common mechanism depending on the environment and the type of an immune response. Further, Treg-mediated suppression is a multi-step process and impairment or augmentation of each step can alter t... International Immunology journals http://www.medworm.com/rss/comments.php?id=2825559 Wed, 23 Sep 2009 23:00:00 +0100 2825559 http://www.medworm.com/index.php?rid=2825558&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2F1101%3Frss%3D1 Immune regulation plays an important role in maintaining homeostasis of the immune system. A number of Japanese immunologists have made significant contributions to the elucidation of the mechanisms of immune regulation. In particular, lymphocyte populations that could regulate immune responses—for example regulatory T cells and NKT cells—have been extensively analyzed. Here, we present an overview of research on immune regulation by highlighting the work of several Japanese contributors. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2825558 Wed, 23 Sep 2009 23:00:00 +0100 2825558 http://www.medworm.com/index.php?rid=2825557&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F10%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2825557 Wed, 23 Sep 2009 23:00:00 +0100 2825557 http://www.medworm.com/index.php?rid=2731273&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1089%3Frss%3D1 Human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell leukemia, HTLV-I-associated myelopathy/tropical spastic paraparesis and various autoimmune-like disorders. T-cell immune suppression is also associated with HTLV-I infection. Mechanisms of diverse immune dysregulation in HTLV-I infection are obscure. Here, we investigated a potential link between autoimmunity and immune suppression in HTLV-I infection. G14, an IL-2-dependent HTLV-I-negative CD4+CD8+ T-cell line previously established from an HTLV-I-infected rat, constantly proliferated and produced IFN-. IFN- production by G14 cells was dependent on interactions between CD4 and MHC-II, suggesting that G14 cells recognized self-antigens presented by MHC-II on themselves. To examine immune response to G14 cells, we i... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731273 Mon, 24 Aug 2009 23:00:00 +0100 2731273 http://www.medworm.com/index.php?rid=2731272&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1079%3Frss%3D1 The IL-7R controls local accessibility of joining (J) gene segments in the mouse TCR locus by recruiting signal transducers and activators of transcription (STAT) 5 and transcriptional coactivators to the J germ line promoters and inducing histone acetylation and germ line transcription. Because STAT consensus motifs are conserved not only in the J promoters but also in the TCR 3' enhancer (E) elements, it is possible that STAT5 interacts with and activates E. To address this question, we first showed that the lysine 4 residue of histone H3 is substantially methylated at E1 and E4 elements in wild-type early thymocytes and that the levels of the methylation are reduced in IL-7R chain-deficient mice. We also showed that STAT5 has potential to elevate histone acetylation of the E elements in... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731272 Mon, 24 Aug 2009 23:00:00 +0100 2731272 http://www.medworm.com/index.php?rid=2731271&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1065%3Frss%3D1 Regulatory CD4+CD25Hi T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. However, the underlying mechanisms by which they impact antigen-specific CD8+ immune responses in cancer patients and how they interact with each other under physiologic conditions remain unclear. Herein, we examined the relationship of PD-1 and its abrogation to the function of Treg in patients with melanoma using short-term in vitro assays to generate melanoma-specific T cells. We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients’ peripheral blood. Programmed death ligand (PD-L) 1 expression was also detected on pat... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731271 Mon, 24 Aug 2009 23:00:00 +0100 2731271 http://www.medworm.com/index.php?rid=2731270&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1057%3Frss%3D1 Intravenous immunoglobulins (IVIg) preparations can be beneficial therapeutic agents for the treatment of tumor metastases as has been shown in both human and animal studies. Operating mechanisms have not yet been completely elucidated. Some of the mechanisms proposed entail the stimulation of the production of IL-12, a cytokine that exhibits anti-angiogenic activities, as well as inhibition of endothelial cells proliferation and vascular endothelial growth factor (VEGF) secretion. The aim of the present study was to investigate whether in an IVIg preparation there are natural antibodies directed against VEGF with the potential to affect angiogenesis. Using both sandwich and direct ELISA assays, IVIg was found to specifically recognize and bind VEGF in a dose-dependent manner. The binding ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731270 Mon, 24 Aug 2009 23:00:00 +0100 2731270 http://www.medworm.com/index.php?rid=2731269&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1047%3Frss%3D1 Peritoneal B cells represent a heterogeneous mixture of mature peripheral B lineage subsets with distinct developmental and functional characteristics. Here, we report that a single intraperitoneal injection of intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester (CFSE) results in the stable fluorescent labeling of resident lymphocytes, without dissipation of the tracer compound into other peripheral lymphoid organs. Using this in situ labeling procedure followed by multicolor flow cytometry or tissue fluorescence at various periods for up to 4 weeks post-labeling, we demonstrate that the distinct peritoneal leukocyte sub-populations and, within the B lineage, B-1 and B-2 B-cell subsets have different exchange kinetics with extraperitoneal sites under steady-state ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731269 Mon, 24 Aug 2009 23:00:00 +0100 2731269 http://www.medworm.com/index.php?rid=2731268&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1037%3Frss%3D1 Celiac disease (CD) is a multifactorial disorder influenced by environmental, genetic and immunological factors. Increasing evidence showed CTLA-4 gene as an important susceptibility locus for autoimmune disorders. A native soluble cytotoxic T-lymphocyte-associated protein-4 (sCTLA-4), lacking of transmembrane sequence, has been described in several autoimmune diseases. We aimed to evaluate the presence of increased sCTLA-4 concentration in the serum of patients with CD and the possible immunoregulatory function. Blood samples were collected from 160 CD patients; sCTLA-4 levels were evaluated by ELISA, western blot and reverse transcription–PCR. The capability of serum sCTLA-4 to modulate T-lymphocyte proliferation in vitro was evaluated by two-way mixed leukocyte reaction assay. We ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731268 Mon, 24 Aug 2009 23:00:00 +0100 2731268 http://www.medworm.com/index.php?rid=2731267&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1025%3Frss%3D1 In this study, we explored the potential of human naive CD4+ T cells to acquire regulatory properties upon stimulation. We demonstrated that, in vitro, pre-activated naive CD4+CD25–CD45RA+ T cells could become anergic and suppressive CD4+CD25+ T cells upon lower intensity TCR stimulation. These CD4+CD25+ T cells generated in vitro potently suppress the proliferation of allogenic CD4+CD25– T cells independently of cytokines and in a contact-dependent manner. Our data indicate that expression of Foxp3 is not necessary to induce the suppressive T cell activity. We demonstrate that these CD4+CD25+ T cells are unresponsive upon re-stimulation and that their suppressive activity is transient. However, we showed that the anergy and the suppressive function could be reversed by increas... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731267 Mon, 24 Aug 2009 23:00:00 +0100 2731267 http://www.medworm.com/index.php?rid=2731266&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1013%3Frss%3D1 Human colostrum contains many bioactive factors that must promote the development of intestinal mucosal immunity in infants. Especially, the presence of certain cytokines such as transforming growth factor (TGF)-β or IL-10 has been of great interest for IgA production as a function of mucosal immune response. In the present study, we attempted to investigate whether unidentified factors inducing generation of IgA-producing cells from naive B cells might exist in colostrum. For this purpose, colostrum samples were directly added to a culture consisting of naive B cells and dendritic cells from cord blood and CD40 ligand-transfected L cells, comparing with recombinant IL-10 (rIL-10) and/or rTGF-β. It was noted that most colostrum samples alone were able to induce IgA-secreting cell... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731266 Mon, 24 Aug 2009 23:00:00 +0100 2731266 http://www.medworm.com/index.php?rid=2731265&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2F1003%3Frss%3D1 Understanding primary immunodeficiencies has elucidated many aspects of human immunity and susceptibility to infections. Recently, defects have been identified that result in deficiencies of terminally differentiated subsets of lymphocytes including deficiencies of memory B cells, NKT cells and Th17 T cells. Together with defects specific to Th1 responses, these disorders revealed that dedicated pathogen-specific mechanisms exist for prevalent human pathogens, and that some host defence strategies are remarkably specific. Deficiency of Th17 cells confirms that this subset of effector T cells is important for defence at epithelial surfaces. The clinical phenotype includes devastating complications from infection with Staphylococcus aureus. Since the microbial load at human epithelial surfac... International Immunology journals http://www.medworm.com/rss/comments.php?id=2731265 Mon, 24 Aug 2009 23:00:00 +0100 2731265 http://www.medworm.com/index.php?rid=2731264&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F9%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2731264 Mon, 24 Aug 2009 23:00:00 +0100 2731264 http://www.medworm.com/index.php?rid=2641996&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F991%3Frss%3D1 In this study, we report for the first time that murine bone marrow-derived mast cells (BMMC) express messenger RNA and protein for CCR1. BMMC cultured in the presence of murine recombinant stem cell factor and murine IL-3 expressed CCR1 after 5–6 weeks. We also report for the first time that mBMMCCCR1+ cells endogenously express neurokinin receptor-1 and intercellular adhesion molecule-1. To examine the activity of CCR1 on these BMMC, we simultaneously stimulated two receptors: CCR1 by its ligand macrophage inflammatory protein-1 and the IgE receptor FcRI by antigen cross-linking. We found that co-stimulation enhanced BMMC degranulation compared with FcRI stimulation alone, as assessed by β-hexosaminidase activity (85 versus 54%, P < 0.0001) and Ca2+ influx (223 versus 183 n... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641996 Sun, 26 Jul 2009 23:00:00 +0100 2641996 http://www.medworm.com/index.php?rid=2641995&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F977%3Frss%3D1 Peripheral naive CD4+ T cells selectively differentiate to type 1 Th, type 2 Th and IL-17-producing Th (Th17) cells, depending on the priming conditions. Since these subsets develop antagonistically to each other to elicit subset-specific adaptive immune responses, balance between these subsets can regulate the susceptibility to diverse immune diseases. The present study was undertaken to determine whether poly--glutamic acid (-PGA), an edible and safe exopolymer that is generated by microorganisms such as Bacillus subtilis, could modulate the development pathways of Th subsets. The presence of -PGA during priming promoted the development of Th1 and Th17 cells but inhibited development of Th2 cells. -PGA up-regulated the expression of T-bet and ROR-t, the master genes of Th1 and Th17 cells... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641995 Sun, 26 Jul 2009 23:00:00 +0100 2641995 http://www.medworm.com/index.php?rid=2641994&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F967%3Frss%3D1 In this study, we aimed to identify novel genes involved in experimental and human asthma, importance of which has not yet been recognized. In an ovalbumin-induced murine model of asthma, we applied microarray gene expression analysis at different time points after allergen challenges. Advanced statistical methods were used to relate gene expression changes to cellular processes and to integrate our results into multiple levels of information available in public databases. At 4 h after the first allergen challenge, gene expression pattern reflected mainly an acute, but non-atopic, inflammatory response and strong chemotactic activity. At 24 h after the third allergen challenge, gene set enrichment analysis revealed significant over-representation of gene sets corresponding to Th2-type infl... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641994 Sun, 26 Jul 2009 23:00:00 +0100 2641994 http://www.medworm.com/index.php?rid=2641993&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F957%3Frss%3D1 Recently, we identified that diverse heavy chain (H-chain)-only IgG is spontaneously produced in light chain (L-chain)-deficient mice (L–/– with silenced and loci) despite a block in B cell development. In murine H-chain IgG, the first C exon, CH1, is removed after DNA rearrangement and secreted polypeptides are comparable with camelid-type H-chain IgG. Here we show that L–/– mice generate a novel class of H-chain Ig with covalently linked chains, not identified in any other healthy mammal. Surprisingly, diverse H-chain-only IgA can be released from B cells at levels similar to conventional IgA and is found in serum and sometimes in milk and saliva. Surface IgA without L-chain is expressed in B220+ spleen cells, which exhibited a novel B cell receptor, suggesting th... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641993 Sun, 26 Jul 2009 23:00:00 +0100 2641993 http://www.medworm.com/index.php?rid=2641992&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F947%3Frss%3D1 The DNA cleavage step in both the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes is initiated by activation-induced cytidine deaminase (AID). However, the detailed mechanisms of the DNA strand cleavage in SHM and CSR are still largely unknown. Recently, the apurinic/apyrimidinic endonucleases, Apex1 and Apex2, were reported to be involved in the DNA cleavage step of CSR. Here, we examined the role of Apex2 in SHM using Apex2-deficient mice and found that the Apex2 deficiency caused a drastic reduction in the frequency of SHM and the number of mutations per mutated clone without affecting the pattern of base substitution. These results suggest that Apex2 may play a critical role in SHM through its 3'–5' exonuclease activity. Unexpectedly, the efficiency o... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641992 Sun, 26 Jul 2009 23:00:00 +0100 2641992 http://www.medworm.com/index.php?rid=2641991&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F935%3Frss%3D1 Abzymes (Abzs) with different enzymic activities have been detected in the sera of patients with various autoimmune (AI) diseases and in AI mice. In this work, electrophoretically homogeneous IgGs were isolated from the sera of MRL-lpr/lpr mice spontaneously developing lupus-like AI pathology. It was shown for the first time that polyclonal IgGs (pIgGs) and their isolated heavy and light chains hydrolyze different nucleoside-5'-triphosphate (NTPs), nucleoside-5'-diphosphate (NDPs), adenosine monophosphate and deoxiadenosine-5'-monophosphate (dAMP), whereas antibodies from the sera of control healthy mice were catalytically inactive. Monoclonal mouse IgGs also effectively hydrolyze nucleotides. The data demonstrate that nucleotide-hydrolyzing activity is an intrinsic property of isolated mo... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641991 Sun, 26 Jul 2009 23:00:00 +0100 2641991 http://www.medworm.com/index.php?rid=2641990&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F925%3Frss%3D1 This study provides evidence that MD-2 possesses potential ability to play an essential role in cell surface expression of TLR4. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2641990 Sun, 26 Jul 2009 23:00:00 +0100 2641990 http://www.medworm.com/index.php?rid=2641989&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F913%3Frss%3D1 Antibodies specific to moesin, which are frequently detectable in the serum of patients with aplastic anemia (AA), can induce tumor necrosis factor- (TNF-) secretion from monocytes and a human monocytic leukemia cell line THP-1. We investigated the mechanisms responsible for TNF- secretion from monocytic cells induced by the auto-antibodies that are purified from the sera of AA patients. TNF- induction by anti-moesin antibodies depended on the amount of cell surface moesin expressed by THP-1 cells. F(ab')2 fragments prepared from the anti-moesin antibodies were able to stimulate THP-1 cells to secrete TNF- and this stimulatory effect was enhanced by cross-linking of moesins with anti-human IgG F(ab')2 fragment antibodies. Anti-moesin antibodies as well as their F(ab')2 fragments induced th... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641989 Sun, 26 Jul 2009 23:00:00 +0100 2641989 http://www.medworm.com/index.php?rid=2641988&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F905%3Frss%3D1 In this study, to clarify the protective mechanism of CAP11 against endotoxin shock, we evaluated the effects of CAP11 on the production and release of septic mediators in vitro and in vivo using a murine macrophage cell line RAW264.7 and a D-galactosamine-sensitized murine endotoxin shock model. LPS stimulation induced the production of inflammatory cytokines and anandamide and release of HMGB1 from RAW264.7 cells. Importantly, CAP11 suppressed the LPS-induced production and release of these mediators by RAW264.7 cells. Moreover, LPS administration enhanced the serum levels of HMGB1, anandamide and inflammatory cytokines in the endotoxin shock model. Of note, CAP11 suppressed the LPS-induced increase of these mediators in sera, and LPS binding to CD14-positive cells (peritoneal macrophage... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641988 Sun, 26 Jul 2009 23:00:00 +0100 2641988 http://www.medworm.com/index.php?rid=2641987&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2F891%3Frss%3D1 CD70 expressed on dendritic cells (DCs) has been shown to play a critical role in inducing effective CD8+ T cell responses and a Th1 response in mice. However, it has not been extensively examined whether human primary DCs express CD70 and whether the CD70–CD27 interaction promotes naive CD4+ T cells to acquire the ability to produce effector cytokines during the DC–T cell interaction in humans. Here, we show that human myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells stimulated with CD40 ligand together with pro-inflammatory cytokines or Toll-like receptor ligands express CD70. Thymic stromal lymphopoietin plus prostaglandin E2 also induced CD70 on mDCs. Naive CD4+ T cells stimulated with DCs but not with anti-CD3/CD28 microbeads expressed CD70. Stimulation with... International Immunology journals http://www.medworm.com/rss/comments.php?id=2641987 Sun, 26 Jul 2009 23:00:00 +0100 2641987 http://www.medworm.com/index.php?rid=2641986&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F8%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2641986 Sun, 26 Jul 2009 23:00:00 +0100 2641986 http://www.medworm.com/index.php?rid=2485600&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F881%3Frss%3D1 In this study, we found that expression of the growth factor independent 1 (Gfi1) gene, which has been implicated in Th2 development, was repressed in Th17 and iTreg cells compared with Th1 and Th2 lineages. Gfi1 expression was enhanced by the IFN-/STAT1 and IL-4/STAT6 pathways, whereas it was repressed by the transforming growth factor-β1 stimulation at the promoter level. Over-expression of Gfi1 strongly reduced IL-17A transcription in the EL4 T cell line, as well as in primary T cells. This was due to the blockade of recruitment of retinoid-related orphan receptor t to the IL-17A promoter. In contrast, IL-17A expression was significantly enhanced in Gfi1-deficient T cells under Th17-promoting differentiation conditions as compared with wild-type T cells. In contrast, the impacts of... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485600 Sat, 20 Jun 2009 23:00:00 +0100 2485600 http://www.medworm.com/index.php?rid=2485599&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F871%3Frss%3D1 In this study, we have compared uptake of antigen by mouse DC in the presence of different Toll-like receptor (TLR) agonists, which are potent inducers of DC activation. Here we show that the reduction in uptake of soluble antigen in the presence of the viral double-stranded RNA (dsRNA) analogues polyinosinic–polycytidylic acid and Ampligen is independent of TLR-mediated DC activation. A reduction in antigen uptake by bone marrow-derived and splenic DC was also observed in response to other RNA homopolymers such as polyinosinic and polyguanylic acids, which are known inhibitors of scavenger receptor-mediated endocytosis. Pinocytosis and mannose receptor-mediated uptake of soluble antigen were not affected by any of the tested nucleic acids. The reduction in antigen uptake by dsRNA di... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485599 Sat, 20 Jun 2009 23:00:00 +0100 2485599 http://www.medworm.com/index.php?rid=2485598&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F859%3Frss%3D1 The role of invariant NKT (iNKT) cells in reactive arthritis is unknown. We explored the functional role of NKT cells in reactive arthritis using an established murine model of Chlamydia trachomatis-induced arthritis (CtIA). CtIA in wild-type and CD1d knockout (KO) mice was induced by intra-articular injection of C. trachomatis. The effect of -galactosylceramide (-GalCer) activation of iNKT cells was investigated by intra-peritoneal administration of -GalCer. Histopathological and phenotypic changes, chlamydial clearance and cytokine and chemokine production in synovial tissue of the knee joint were investigated after onset of the arthritis. The severity of CtIA was significantly increased in CD1d KO mice, which was associated with decrease in bactericidal cytokine IFN-, regulatory cytokin... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485598 Sat, 20 Jun 2009 23:00:00 +0100 2485598 http://www.medworm.com/index.php?rid=2485597&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F843%3Frss%3D1 ‘Humanized mice’ are anticipated to be a valuable tool for studying the human immune system, but the reconstituted human immune cells have not yet been well characterized. Here, we extensively investigated the differentiation and functions of human B and T cells in a supra-immunodeficient mouse strain, NOD/shi-scid/cnull (NOG) reconstituted with CD34+ hematopoietic stem cells obtained from umbilical cord blood. In these hu-HSC NOG mice, the development of human B cells was partially blocked, and a significant number of B-cell progenitors accumulated in the spleen. The mature CD19+IgM+IgD+ human B cells of the hu-HSC NOG mice could produce IgG in vivo and in vitro by antigenic stimulation. In contrast, although human T cells with an apparently normal phenotype developed, most of... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485597 Sat, 20 Jun 2009 23:00:00 +0100 2485597 http://www.medworm.com/index.php?rid=2485596&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F831%3Frss%3D1 B cell antigen receptor (BCR) cross-linking promotes proliferation and survival of mature B cells. Phosphoinositide-3-kinase-mediated down-regulation of pro-apoptotic and anti-mitogenic genes such as the Foxo family of transcription factors is an important component of this process. Previously, we demonstrated that BCR signaling decreases expression of transcripts for Foxo1, Foxo3 and Foxo4. We now show that BCR-induced down-regulation of Foxo3 and Foxo4 mRNA expression occurs via distinct mechanisms from those established for Foxo1. While Foxo1, Foxo3 and Foxo4 bind the same DNA sequence, the differential control of their expression upon B cell activation suggests that they may have unique functions in the B lineage. To begin to address this issue, we evaluated B cell development and func... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485596 Sat, 20 Jun 2009 23:00:00 +0100 2485596 http://www.medworm.com/index.php?rid=2485595&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F817%3Frss%3D1 Myocardial ischemia with subsequent reperfusion (MI/R) can lead to significant myocardial damage. Ischemia initiates inflammation at the blood–microvascular endothelial cell interface and contributes significantly to both acute injury and repair of the damaged tissue. We have found that MI/R injury in mice is associated with a cellular immune response to troponin. Myocardial cells exclusively synthesize troponin and release the troponin into the bloodstream following injury. Mucosally administered proteins induce T cells that secrete anti-inflammatory cytokines such as IL-10 and transforming growth factor β at the anatomical site where the protein localizes. We found that nasal administration of the three subunits of troponin (C, I and T isoforms), given prior to or 1 h followin... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485595 Sat, 20 Jun 2009 23:00:00 +0100 2485595 http://www.medworm.com/index.php?rid=2485594&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F803%3Frss%3D1 Over-expression of PU.1, a myeloid- and lymphoid-specific transcription factor belonging to the Ets family, induces monocyte-specific gene expression in mast cells. However, the effects of PU.1 on each target gene and the involvement of cytokine signaling in PU.1-mediated gene expression are largely unknown. In the present study, PU.1 was over-expressed in two different types of bone marrow-derived cultured mast cells (BMMCs): BMMCs cultured with IL-3 plus stem cell factor (SCF) and BMMCs cultured with pokeweed mitogen-stimulated spleen-conditioned medium (PWM-SCM). PU.1 over-expression induced expression of MHC class II, CD11b, CD11c and F4/80 on PWM-SCM-cultured BMMCs, whereas IL-3/SCF-cultured BMMCs expressed CD11b and F4/80, but not MHC class II or CD11c. When IFN- was added to the IL-... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485594 Sat, 20 Jun 2009 23:00:00 +0100 2485594 http://www.medworm.com/index.php?rid=2485593&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F793%3Frss%3D1 In this study, we show that melanoma cell lines are highly heterogeneous for the expression of several stem cell-associated markers including CD133, c-kit/CD117 and p75 neurotrophin receptor/CD271. Since no information is available on the ability of NK cells to recognize and lyse melanoma stem cells, we assessed whether melanoma cell lines, characterized by stem cell-like features, were susceptible to lysis by IL-2-activated NK cells. We show that activated NK cells efficiently kill malignant melanoma cell lines that were enriched in putative CSC by the use of different selection methods (i.e. CD133 expression, radioresistance or the ability to form melanospheres in stem cell-supportive medium). NK cell-mediated recognition and lysis of melanoma cells involved different combinations of act... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485593 Sat, 20 Jun 2009 23:00:00 +0100 2485593 http://www.medworm.com/index.php?rid=2485592&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F779%3Frss%3D1 Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latency are needed in order to improve Mth control. In order to analyze if perturbations of peripheral NK cells may be associated with exit from Mth latency, sequential patients with newly diagnosed lung tuberculosis (TB) were studied. Peripheral NK cells were analyzed by cytofluorometry, in vitro culture and functional assays. At the onset of lung TB, imbalances in NK cell subsets were evident. Decreased CD56brightCD16+/– subsets with significantly compromised NKp30 and NKp46 expression and with specifically decreased -IFN production upon triggering were evident. These features were not completely restored when purified NK cells were cultured in vitro. Culture supplementation with -IFN increas... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485592 Sat, 20 Jun 2009 23:00:00 +0100 2485592 http://www.medworm.com/index.php?rid=2485591&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F769%3Frss%3D1 The ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) has been implicated in various immune functions. Our previous studies have shown that AhR activation by exposure of ovalbumin (OVA)-immunized mice to the potent ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases immunization-induced IFN- production in the spleen and suppresses the production of Th2 cytokines and OVA-specific antibodies. In the present study, we used transgenic (Tg) mice that express a constitutively active mutant of aryl hydrocarbon receptor (CA-AhR) specifically in T-lineage cells to clarify the role of AhR activation in T cells in these reactions. The results of this study clearly demonstrated that AhR activation only in the T cells augments IFN- production upon OVA immunization. By contra... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485591 Sat, 20 Jun 2009 23:00:00 +0100 2485591 http://www.medworm.com/index.php?rid=2485590&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2F757%3Frss%3D1 Although it is well documented that the immunological activity of cytosine–guanine (CpG) motifs is abrogated by 5' methylation of the cytosine residue, encapsulation within stabilized lipid nanoparticles endows these methylated cytosine–guanine- (mCpG-) containing oligonucleotides (ODNs) with potent immunostimulatory activity in murine animal models. Surprisingly, not only do liposomal nanoparticulate (LN) mCpG ODN possess immunostimulatory activity, their potency is found to be equivalent and often greater than the equivalent unmethylated form, as judged by a number of ex vivo innate and adaptive immune parameters and anti-tumor efficacy in murine models. Preliminary data indicate that both methylated and unmethylated CpG ODN act through a common receptor signaling pathway, sp... International Immunology journals http://www.medworm.com/rss/comments.php?id=2485590 Sat, 20 Jun 2009 23:00:00 +0100 2485590 http://www.medworm.com/index.php?rid=2485589&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F7%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2485589 Sat, 20 Jun 2009 23:00:00 +0100 2485589 http://www.medworm.com/index.php?rid=2437083&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F745%3Frss%3D1 Reports that follicular dendritic cells (FDCs) produce IL-6 prompted the hypotheses that immune complexes (ICs) induce FDCs to produce IL-6 and that FDC–IL-6 promotes germinal center (GC) reactions, somatic hypermutation (SHM) and IgG production. FDCs were activated in vitro by addition of ICs and FDC–IL-6 production was determined. Wild-type (WT) and IL-6 knockout (KO) mice, as well as chimeras with WT and IL-6 KO cells, were immunized with (4-hydroxy-3-nitrophenyl)-acetyl (NP)–chicken gamma globulin (CGG) and used to study anti-(4-hydroxy-3-iodo-5-nitrophenyl) acetyl (NIP) responses, GC formation and SHM in the VH186.2 gene segment in Ig-gamma. FDC–IL-6 increased when FDCs encountered ICs. At low immunogen dose, 1 µg NP–CGG per mouse, the IgG anti-NIP ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437083 Tue, 26 May 2009 04:00:00 +0100 2437083 http://www.medworm.com/index.php?rid=2437082&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F727%3Frss%3D1 Dysregulated generation and/or function of naturally occurring ‘CD4+CD25+ regulatory T cells’ (Tregs) play key role in the development of autoimmune diseases, including type 1 diabetes. Recent findings suggest that Notch3 signaling activation promotes thymic generation and peripheral expansion and in vivo function of naturally occurring Tregs, thus preventing autoimmune diabetes progression in mouse models. However, the mechanisms underlying these effects have remained elusive, thus far. Here, we show that the expression of pT gene is up-regulated in naturally occurring Tregs, at both mRNA and protein levels. Moreover, by using double mutant mice, with T cell-targeted constitutive activation of Notch3 in a pT–/– background, we demonstrate that pT deletion significan... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437082 Tue, 26 May 2009 04:00:00 +0100 2437082 http://www.medworm.com/index.php?rid=2437081&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F715%3Frss%3D1 IL-7 is pivotal for B cell development. Proteins of the Bcl-2 family are essential regulators of lymphocyte survival. Particularly, the pro-apoptotic BH3-only members Bim and Puma mediate lymphocyte apoptosis provoked by cytokine deprivation. Herein, we addressed whether the absence of Bim or Puma within the hematopoietic compartment could bypass the requirement for IL-7-driven B cell development in adult mice. We found that deficiency of Bim, but not Puma, partially rescued B cell development in the absence of IL-7. The numbers of both sIgM– and sIgM+ B cells were markedly increased in the bone marrow of recipients lacking IL-7 upon reconstitution with Bim-deficient hematopoietic progenitors, compared with their control or Puma-deficient counterparts. The augmentation of B cell lymp... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437081 Tue, 26 May 2009 04:00:00 +0100 2437081 http://www.medworm.com/index.php?rid=2437080&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F705%3Frss%3D1 The goal was to identify HLA-DQ8-bound β cell epitopes important in the T cell response in autoimmune diabetes. We first identified HLA-DQ8 (DQA1*0301/DQB1*0302) β cell epitopes using a computational approach and then related their identification to CD4 T cell responses. The computational program (TEA-DQ8) was adapted from one previously developed for identifying peptides bound to the I-Ag7 molecule and based on a library of naturally processed peptides bound to HLA-DQ8 molecules of antigen-presenting cells. We then examined experimentally the response of NOD.DQ8 mice immunized with peptides derived from the Zinc transporter 8 protein. Log-of-odds scores on peptides were experimentally validated as an indicator of peptide binding to HLA-DQ8 molecules. We also examined previously ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437080 Tue, 26 May 2009 04:00:00 +0100 2437080 http://www.medworm.com/index.php?rid=2437079&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F691%3Frss%3D1 In this study, we analyzed the physiological function of Nit1 in T cells using Nit1-knockout mice. Nit1-deficient T cells can undergo apoptosis induced by DNA damage due to irradiation and chemical treatment. However, apoptosis induced by Fas or Ca++ signals appeared to be compromised. Additionally, Nit1 deficiency resulted in T cell hyperproliferative responses induced by TCR stimulation. The expressions of T cell activation markers were elevated in Nit1–/– T cells. There was a spontaneous cell cycle entry and enhanced cell cycle progression in Nit1–/– T cells. These data indicate that Nit1 is a novel negative regulator in primary T cells. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2437079 Tue, 26 May 2009 04:00:00 +0100 2437079 http://www.medworm.com/index.php?rid=2437078&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F679%3Frss%3D1 Recent studies have suggested that statins, the inhibitors for 3-hydroxy-3-methyglutaryl (HMG)-CoA reductase in the mevalonate pathway, exhibit anti-inflammatory effects. However, the immune modulatory effects of statins on the differentiation of CD4+ T cells and their underlying mechanisms are still largely unknown. To address these issues, we examined the effect of simvastatin and inhibitors for protein farnesylation and geranylgeranylation on the differentiation of IL-17-producing T cells (Th17 cells) and Foxp3+ CD4+ T cells. Simvastatin inhibited the differentiation of Th17 cells through the inhibition of HMG-CoA reductase activity but enhanced the differentiation of Foxp3+ CD4+ T cells. Geranylgeranyltransferase I inhibitor, GGTI-298, but not farnesyltransferase inhibitor, FTI-277, mi... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437078 Tue, 26 May 2009 04:00:00 +0100 2437078 http://www.medworm.com/index.php?rid=2437077&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F667%3Frss%3D1 Lysophosphatidic acid (LPA) is an activator and chemoattractant of NK cells, which are critical members of the immunological tumor surveillance machinery. Here, we analyzed the influence of LPA on the interaction of human NK cells with tumor cells such as the Burkitt lymphoma cell line Raji and the human melanoma cell line A2058. Thereby we found that LPA inhibits the release of perforin and cytotoxic activity of NK cells. Analysis of signal transduction showed that LPA induces common signaling pathways of chemotaxins such as Gi protein-dependent actin re-organization, activation of the mitogen-activated protein kinase p38 as well as phosphatidylinositol-3-kinase-dependent signal molecules [protein kinase B/Akt and glycogen synthase kinase-3β (GSK-3β)]. In contrast to most chemot... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437077 Tue, 26 May 2009 04:00:00 +0100 2437077 http://www.medworm.com/index.php?rid=2437076&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F655%3Frss%3D1 In the present study, we investigated the possibility to use irradiated, non-replicating class II transcriptional activator (CIITA)-transfected tumor TS/A cells as a cell-based vaccine. Eighty-three percent of TS/A-CIITA-vaccinated mice were completely protected from tumor growth and the remaining 17% displayed significant reduction of tumor growth. In contrast, only 30% of mice injected with irradiated TS/A parental cells were protected from tumor growth, whereas the remaining 70% of animals remained unprotected. Immunity generated in the TS/A-CIITA-vaccinated mice correlated with an efficient priming of CD4+ T cells and consequent triggering and maintenance of CD8+ CTL effectors, as assessed by adoptive transfer assays. Important qualitative differences were observed between the two cell... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437076 Tue, 26 May 2009 04:00:00 +0100 2437076 http://www.medworm.com/index.php?rid=2437075&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F645%3Frss%3D1 A major neurotransmitter dopamine transmits signals via five different seven transmembrane G protein-coupled receptors termed D1–D5. It is now evident that dopamine is released from leukocytes and acts as autocrine or paracrine immune modulator. However, the role of dopamine for dendritic cells (DCs) and Th differentiation remains unclear. We herein demonstrate that human monocyte-derived dendritic cells (Mo-DCs) stored dopamine in the secretary vesicles. The storage of dopamine in Mo-DCs was enhanced by forskolin and dopamine D2-like receptor antagonists via increasing cyclic adenosine 3',5'-monophosphate (cAMP) formation. Antigen-specific interaction with naive CD4+ T cells induced releasing dopamine-including vesicles from Mo-DCs. In naive CD4+ T cells, dopamine dose dependently i... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437075 Tue, 26 May 2009 04:00:00 +0100 2437075 http://www.medworm.com/index.php?rid=2437074&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F633%3Frss%3D1 Humans vary markedly in their propensity to develop asthma, despite often being exposed to similar environmental stimuli. Similarly, mouse strains vary in susceptibility to airways pathology in experimental asthma. Sensitization and aerosol challenge with ovalbumin (OVA) induces eosinophil accumulation, mucus production and airways obstruction in BALB/c and C57BL/6 mice. In contrast, CBA/Ca mice show relatively little pathology. Allergen-induced production of IL-4, IL-5, IL-10 and IFN- was detected in all three strains, with BALB/c mice generating the highest levels of IL-4, IL-5 and IL-10. Microarray analysis was used to identify genes differentially regulated in lung tissue after OVA challenge. Differentially regulated genes in the lungs of the asthma-susceptible C57BL/6 and BALB/c strai... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437074 Tue, 26 May 2009 04:00:00 +0100 2437074 http://www.medworm.com/index.php?rid=2437073&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2F621%3Frss%3D1 Mast cells are bone marrow-derived effector cells that can initiate inflammatory responses to infectious organisms or allergens by releasing a multitude of pro-inflammatory factors including prostaglandin (PG) D2. We demonstrate that primary murine bone marrow-derived mast cells (BMMCs) express the PGD2 receptor; chemoattractant receptor-homologous molecule expressed on Th class 2 cells (CRTh2). Activation of CRTh2 on BMMC by PGD2 or the CRTh2-specific agonist, 13,14-dihydro-15-keto-prostaglandin D2 (DK-PGD2), resulted in signaling response including Ca2+ mobilization and phosphorylation of the p42/p44 extracellular signal-regulated kinases (ERKs) kinases. Phosphorylation of the ERKs could be blocked by pertussis toxin, as well as a small molecule antagonist of CRTh2, Compound A. Activatio... International Immunology journals http://www.medworm.com/rss/comments.php?id=2437073 Tue, 26 May 2009 04:00:00 +0100 2437073 http://www.medworm.com/index.php?rid=2437072&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F6%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2437072 Tue, 26 May 2009 04:00:00 +0100 2437072 http://www.medworm.com/index.php?rid=2370105&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F607%3Frss%3D1 The ability of the host to distinguish between self and foreign nucleic acids is one of the critical factors contributing to the recognition of pathogens by Toll-like receptors (TLRs). Under certain circumstances, eukaryotic self-RNA may reach TLR-containing compartments allowing for self-recognition. Specific modifications were previously demonstrated to suppress immune activation when placed at several positions in an immune stimulatory RNA or silencing RNA (siRNA). However, we show that even a simple natural modification such as a single 2'-O-methylation at different nucleotide positions throughout a sequence derived from a self-RNA strongly interferes with TLR-mediated effects. Such a single modification can even have an inhibitory effect in vitro and in vivo when placed in a different... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370105 Tue, 28 Apr 2009 04:00:00 +0100 2370105 http://www.medworm.com/index.php?rid=2370104&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F599%3Frss%3D1 NK cell recognition of cells that do not express or express low amounts of MHC class I molecules results not only in direct killing of target cells but also in the generation of specific T cell responses consequent to the induction of dendritic cell (DC) activation. While IL-12 production by NK cell-activated DCs is generally thought to play a critical role, a similar DC-mediated NK cell help has been reported also in IL-12-knockout mice. Here, we show that human NK cells can induce on DC surface membrane, via IFN- secretion, the expression of high levels of IL-15. Remarkably, we show that DC expression of this membrane-bound form of IL-15, which is only partially associated with IL-15R molecules, is essential to promote specific CD8+ T lymphocyte response in the absence of DC-derived IL-1... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370104 Tue, 28 Apr 2009 04:00:00 +0100 2370104 http://www.medworm.com/index.php?rid=2370103&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F587%3Frss%3D1 Activation of resting T cells in vitro is triggered by combined TCR and CD28 engagement and can be modulated by simultaneous ligation of various other surface receptors. Although the Fas ligand (FasL) is best known for its capacity to initiate cell death in Fas-bearing cells, it has recently been implicated in the regulation of T cell activation. Thus, a cross-talk between the TCR and FasL is likely, but far from being biochemically elucidated. We now report that FasL engagement by immobilized but not soluble FasFc fusion protein and anti-FasL polyclonal antibody blocks the activation of human peripheral T cells even in the presence of CD28 co-stimulation. The data presented here stress the importance of the Fas/FasL system for signal initiation via the TCR–CD3 complex and provide fu... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370103 Tue, 28 Apr 2009 04:00:00 +0100 2370103 http://www.medworm.com/index.php?rid=2370102&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F575%3Frss%3D1 c-Abl is a widely expressed Src family protein tyrosine kinase that is activated by chromosomal translocation in certain human leukemias. While shown in various experimental systems to regulate cell division and stress responses, its biological functions remain poorly understood. Although expressed at similar levels throughout B cell development, we found that the fraction of phosphorylated, active c-Abl peaks at the pro-B stage. We went on to perform a detailed analysis of B cell development in c-Abl-deficient mice. We confirmed a striking but variable decrease in pro- and pre-B cell numbers, a decrease in pre-B cell growth and an increase in pre-B cell apoptosis. This phenotype was not rescued by transgenic expression of a functional IgHC transgene and only partially rescued by the anti-... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370102 Tue, 28 Apr 2009 04:00:00 +0100 2370102 http://www.medworm.com/index.php?rid=2370101&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F567%3Frss%3D1 The introduction of antigen into the anterior chamber (AC) of the eye induces the production of antigen-specific splenic CD8+ regulatory T cells (AC-SPL cells) that suppress a delayed-type hypersensitivity (DTH) reaction in immunized mice. Because the generation of these regulatory T cells is also induced by exposure to transforming growth factor (TGF)-β and antigen or F4/80+ cells exposed to TGF-β and antigen in vitro, we investigated (i) whether these cells are produced in dominant negative receptor for transforming growth factor β receptor type II (dnTGFβRII) or Cbl-b–/– mice whose T cells are resistant to TGF-β, (ii) whether DTH is suppressed by wild type (WT) CD8+ AC-SPL cells in Cbl-b–/– and dnTGFβRII mice and (iii) the effect of ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370101 Tue, 28 Apr 2009 04:00:00 +0100 2370101 http://www.medworm.com/index.php?rid=2370100&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F555%3Frss%3D1 Early activation of the IL-12/IFN- axis has been shown following Salmonella enterica serovar Enteritidis (S. Enteritidis) infection. We were interested to study whether IL-22 and IL-17A production is initiated early in response to S. Enteritidis. We demonstrate here that IL-22 was strongly elevated in the peritoneal lavage fluid and in serum already 1 day post-intraperitoneal infection (d.p.i.) of mice; not only IL-22 but also IL-17A was produced ex vivo by activated peritoneal exudate cells (PEC). Peritoneal T cells were identified as cellular source of IL-17A. The early IL-22 production was completely IL-23-dependent. In contrast, IL-17A production was only partially IL-23-dependent. To investigate the local production of upstream cytokines important for induction of IL-22, IL-17A and IF... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370100 Tue, 28 Apr 2009 04:00:00 +0100 2370100 http://www.medworm.com/index.php?rid=2370099&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F543%3Frss%3D1 Contributions of lipases to CTL function have been debated, including if T cell lipases damage target cells. Expression of the lipase pancreatic lipase-related protein 2 (PLRP2) was previously found in IL-4 cultured lymphocyte cell lines but absent from IL-2 cultured lymphocytes. Here, we evaluated IL-2 and IL-4 induced CTLs for hydrolysis of target cell lipids and killing. Using anti-CD3 redirected lysis of [3H]-oleic acid-labeled P815 tumor cells, we detected the release of the radioactive fatty acid (FA). When PLRP2+/+ and PLRP2–/– CTLs were compared, there was more killing by the PLRP2+/+ CTLs. However, [3H]-oleic acid release was similar per dead P815, suggesting that lipid hydrolysis was produced by the dead P815s rather than by PLRP2. The FA release and death were comple... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370099 Tue, 28 Apr 2009 04:00:00 +0100 2370099 http://www.medworm.com/index.php?rid=2370098&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F533%3Frss%3D1 Binding of various antibody isotypes to B cells through either FcRs or complement receptors has been attributed to play several roles, e.g. in immune complex (IC) transportation and regulation of B cell receptor signaling. We have revealed a novel B cell intrinsic receptor for IgM and IgG which is present in C57BL/6 (B6) mice and is more abundant in non-obese diabetic (NOD) mice. As a consequence, the level of extramembranous IgG monomers and IgM pentamers on peripheral blood B cells from NOD mice was significantly higher compared with B6 mice. The effect of this aberration was that all B cells in peripheral blood of (NOD.IgHa x B6(IgHb))F1 mice carried both IgM allotypes on their surface. In addition, analysis of IC binding using IgG- or IgM-opsonized bacterial particles revealed a higher... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370098 Tue, 28 Apr 2009 04:00:00 +0100 2370098 http://www.medworm.com/index.php?rid=2370097&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F523%3Frss%3D1 The CC chemokine receptor (CCR)4 is associated with trafficking of specialized cutaneous memory type 2 Th cells in the skin. However, a CD8+ T cell population expressing CCR4 still remains uncharacterized. In the present study, we investigated the expression and function of CCR4 on human CD8+ T cells and characterized CCR4+CD8+ human T cells. Multi-color flow cytometric analysis revealed that CCR4+CD8+ T cells were predominantly found in the CD27+CD28+CD45RA– memory subset and expressed the CCR7+/–CCR5– phenotype. CCR4+CD8+ T cells expressed neither perforin (Per) nor granzymes (Gra) A/B, suggesting that they were more immature memory T cells than the CCR6+CD8+ early effector memory T cells that express GraA and Per. CCR4+CD8+ T cells effectively produced IL-4, IFN-, IL-2... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370097 Tue, 28 Apr 2009 04:00:00 +0100 2370097 http://www.medworm.com/index.php?rid=2370096&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F511%3Frss%3D1 Proteoglycan (PG) aggrecan-induced arthritis (PGIA) is a murine model of rheumatoid arthritis (RA). Although BALB/c and DBA/2 mice share the same MHC (H-2d) haplotype, the BALB/c strain is susceptible to PGIA, while DBA/2 mice are resistant. Therefore, these two inbred mouse strains provide an opportunity to study arthritis susceptibility factors excluding the effects of MHC-associated genetic components. The goal of this study was to monitor changes in the cellular composition and activation state following intra-peritoneal (i.p.) immunization to induce PGIA; additionally, we sought to identify new susceptibility factors by comparing PG-induced immune responses in BALB/c and DBA/2 mice. Upon i.p. PG injection, resident naive B1 cells are replaced by both T cells and conventional B cells i... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370096 Tue, 28 Apr 2009 04:00:00 +0100 2370096 http://www.medworm.com/index.php?rid=2370095&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F499%3Frss%3D1 The non-obese diabetic (NOD) mouse strain is prone to developing various autoimmune syndromes including type I diabetes mellitus (T1DM), sialadenitis, thyroiditis and pancreatitis. Although the genetic basis of T1DM has been extensively analyzed, genetic factors that modify the other autoimmune phenotypes are largely unknown. We have recently reported that NOD mice with anti-diabetogenic MHC haplotype (H-2b) and programmed cell death 1 (PD-1) deficiency (NOD.H2b-Pdcd1–/– mice) are protected from T1DM but develop various tissue-specific autoimmune diseases including peripheral neuropathy due to autoimmune neuritis, sialadenitis and gastritis. In the present study, we generated [(C57BL/6 x NOD.H2b)F1 x NOD–H2b]BC1–Pdcd1–/– mice to screen non-MHC quantitati... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370095 Tue, 28 Apr 2009 04:00:00 +0100 2370095 http://www.medworm.com/index.php?rid=2370094&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2F489%3Frss%3D1 Upon activation, naive CD4+ T cells differentiate into different lineages of effector Th subsets. Each subset is characterized by its unique cytokine profile and biological functions. Th17, a newly described Th subset that produces IL-17, IL-17F and IL-22 in preference to other cytokines, has been shown to play an important role in clearing specific pathogens and in inducing autoimmune tissue inflammations. Over the last 2–3 years, significant progress has been made to understand the development and biological functions of Th17 subset. Transforming growth factor β (TGF) together with IL-6 or IL-21 initiates the differentiation while IL-23 stabilizes the generation of Th17 cells. The transcription factors of Th17 cells [retinoid-related orphan receptor (ROR) t, ROR- and signal tr... International Immunology journals http://www.medworm.com/rss/comments.php?id=2370094 Tue, 28 Apr 2009 04:00:00 +0100 2370094 http://www.medworm.com/index.php?rid=2370093&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F5%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2370093 Tue, 28 Apr 2009 04:00:00 +0100 2370093 http://www.medworm.com/index.php?rid=2304188&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F477%3Frss%3D1 The isotype switch defect in CD40–/– mice is corrected by wild-type (WT) CD40 transgene, but not by a mutant CD40 transgene that does not bind tumor necrosis factor receptor-associated factors (TRAF) 2 and 3. To define the individual roles of TRAF2 and TRAF3 in CD40 activation of B cells, we introduced mutant CD40 transgenes that selectively lack the ability to bind TRAF2 (TR2), TRAF3 (TR3) or both (TR2,3) into B cells of CD40–/– mice. Serum IgG1 and IgE levels, IgG1 antibody response to sub-optimal doses of the T cell-dependent antigen keyhole limpet hemocyanin, germinal center formation, CD40-mediated proliferation, isotype switching and activation of the non-canonical NF-B pathway were partially diminished in TR2 and TR3 mice and virtually absent in TR2,3 mice. T... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304188 Wed, 25 Mar 2009 04:00:00 +0100 2304188 http://www.medworm.com/index.php?rid=2304185&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F467%3Frss%3D1 Non-hematopoietic mesenchymal stromal cells in secondary lymphoid organs play pivotal roles in tissue organization and immune responses by exhibiting specialized features such as the production of lymphoid homeostatic chemokines. However, the maturational process of stromal cells mediated by lymphotoxin-beta receptor (LTβR) signaling, a key for stromal maturation, remains unclear. Taking advantage of a stromal cell line established from mouse lymph node, which can produce a homeostatic chemokine, CXC chemokine ligand (CXCL) 13, by the engagement of LTβR but not by tumor necrosis factor (TNF) receptor (TNFR), we analyzed the details of intracellular signaling events during the maturational process. The activation of both canonical and non-canonical nuclear factor-B (NF-B) pathways... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304185 Wed, 25 Mar 2009 04:00:00 +0100 2304185 http://www.medworm.com/index.php?rid=2304182&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F457%3Frss%3D1 In this study, we analyzed the role of Fos-related antigen-1 (Fra-1), another member of the AP-1 family of transcription factors, in LPS-induced responses in RAW264.7 macrophages. Fra-1 was induced in LPS-stimulated macrophages with delayed time kinetics compared with c-Fos. Lentiviral introduction of Fra-1 blocked LPS-induced expression of pro-inflammatory mediators at the protein and mRNA levels. A Fra-1 mutant, which lacks the basic leucine zipper domain required for heterodimer formation and DNA binding, did not inhibit LPS-induced responses. c-Fos bound to the AP-1-binding site early, but afterward it was replaced by Fra-1 in LPS-stimulated macrophages. Over-expression of Fra-1 induced its association with Jun proteins and stable DNA binding from an early time point following LPS stim... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304182 Wed, 25 Mar 2009 04:00:00 +0100 2304182 http://www.medworm.com/index.php?rid=2304178&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F443%3Frss%3D1 L-Selectin (CD62L) mediates T-cell entry into lymph nodes. Whether the microenvironment modulates L-selectin expression of T cells during diapedesis and transit is unknown. Therefore, L-selectin expression was determined quantitatively on circulating T cells in blood, lymph nodes and thoracic duct by confocal laser scanning microscopy. We show that in contrast to leukocyte function-associated antigen-1 (CD11a/CD18) and ICAM-1 (CD54), L-selectin expression is cyclically expressed on recirculating T cells. It is reduced to ~30% of the blood value during entry across high endothelial venules. Within lymph nodes, CD4+ T-cell subsets maintain reduced L-selectin expression at a similar level in all compartments (T-cell zone, B-cell zone and medulla). After exit, L-selectin is re-expressed to lev... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304178 Wed, 25 Mar 2009 04:00:00 +0100 2304178 http://www.medworm.com/index.php?rid=2304175&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F433%3Frss%3D1 Multiple sclerosis (MS) is an inflammatory disease of the central nervous system in which axonal damage and degeneration contribute significantly to the progressive irreversible neurological disability. Similar to pathogenic myelin autoimmunity, autoimmune responses to neuronal antigens may contribute to axonal damage and irreversible disability in MS. Auto-antibodies to the axonal cytoskeletal protein neurofilament light (NF-L) are associated with cerebral atrophy in MS and we have recently reported that NF-L autoimmunity is pathogenic in mice. However, the T-cell response to NF-L in MS patients has not been examined. Here, we identify and characterize T-cell proliferative responses to NF-L as compared with myelin oligodendrocyte glycoprotein (MOG) in MS patients and healthy controls. Usi... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304175 Wed, 25 Mar 2009 04:00:00 +0100 2304175 http://www.medworm.com/index.php?rid=2304172&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F423%3Frss%3D1 NK cell cytotoxicity requires two positive signals for killing of tumors. Activation receptors induce polarization of the microtubule organization center and degranulation, while leukocyte function-associated antigen (LFA)-1 is required for conjugate formation and actin polymerization and under some circumstances may be sufficient for NK cell cytotoxicity. Although the receptor for direct killing of fungi is not known, CD18, the β2 chain of LFA-1, binds components of the capsule and cell wall of the opportunistic pathogen Cryptococcus neoformans, namely the polysaccharides glucoronoxylomannan and galactoxylomannan. Herein, we also demonstrate that LFA-1 was concentrated in regions of the NK cell surface interacting with C. neoformans. Consequently, there was compelling evidence to hyp... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304172 Wed, 25 Mar 2009 04:00:00 +0100 2304172 http://www.medworm.com/index.php?rid=2304169&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F415%3Frss%3D1 In this study, we compared the epitope specificity of anti-topo I auto-antibodies present in sera of dcSSc, lcSSc and SLE patients. We have constructed an antigen fragment library displayed on bacteriophage lambda and screened this library with IgG purified from patients’ sera. Regions of topo I selected from the library were expressed as recombinant fusion proteins and were tested with ELISA and western blot. We unexpectedly found that antibodies against a fragment of topo I {fragment F4 [amino acid (AA)] 451–593} could be detected in sera of healthy individuals and patients with inflammatory rheumatic diseases other than SSc and SLE. Using sera of dcSSc, lcSSc and SLE patients, we showed that the pattern of recognized epitopes is different between these patient groups. Fragme... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304169 Wed, 25 Mar 2009 04:00:00 +0100 2304169 http://www.medworm.com/index.php?rid=2304167&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F403%3Frss%3D1 A role for c-Abl in B cell development and signaling has been suggested by previous work showing that c-Abl-deficient mice have defects in bone marrow B cell development and that c-Abl-deficient B cells are hypoproliferative in response to antigen receptor stimulation. Here we show that in addition to defects in early B cell development, c-Abl-deficient mice have defects in peripheral B cell development, including reduced percentages of peritoneal B-1 cells as well as transitional and marginal zone B cells in the spleen. It has been shown that c-Abl kinase activity increases upon B cell receptor (BCR) stimulation and that one of the targets of tyrosine phosphorylation by c-Abl is CD19. However, the consequences of c-Abl activity on B cell activation and CD19 signaling remain unknown. Here,... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304167 Wed, 25 Mar 2009 04:00:00 +0100 2304167 http://www.medworm.com/index.php?rid=2304164&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F393%3Frss%3D1 The serine/threonine kinase MEKK3, also known as mitogen-activated protein kinase kinase kinase 3, is a critical activator of the transcription factor NF-B in innate immunity. However, the physiological function of MEKK3 in adaptive immunity is unclear. Here we report that following TCR signaling, MEKK3 positively regulated the kinase, IB kinase, leading to NF-B activation. T cells lacking MEKK3 were defective in TCR-induced and cytokine-induced responses. Furthermore, T cell-specific deletion of MEKK3 resulted in reduced numbers of thymocytes and peripheral T cells. Thus, our results provide genetic evidence that MEKK3 plays a crucial role in adaptive immunity. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2304164 Wed, 25 Mar 2009 04:00:00 +0100 2304164 http://www.medworm.com/index.php?rid=2304160&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F379%3Frss%3D1 This report shows that T cell-deficient BALB/c nude mice reconstituted with naive unfractionated T cells are specifically tolerized to DBA/2 skin grafts by DST and anti-CD4 mAb treatment, whereas those transferred with T cell suspensions depleted of all Foxp3+CD25+CD4+ natural regulatory T cells (Tregs) are not. The treatment inhibits Mls-1a allo-antigen-specific expansion of CD4+ non-Tregs expressing Vβ6 TCR subfamily but leaves the expansion of Vβ6-expressing Tregs unaffected, allowing the latter to selectively expand and establish donor-specific tolerance. Furthermore, anti-CD4 mAb inhibits in vitro the selective expansion of allo-antigen-specific CD4+ non-Tregs but not natural Tregs, as observed with in vitro anti-CD154 [CD40 ligand (CD40L)] mAb or rapamycin treatment. The re... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304160 Wed, 25 Mar 2009 04:00:00 +0100 2304160 http://www.medworm.com/index.php?rid=2304157&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F361%3Frss%3D1 Retinoic acid (RA) produced by intestinal dendritic cells (DCs) imprints gut-homing specificity on lymphocytes and enhances Foxp3+ regulatory T-cell differentiation. The expression of aldehyde dehydrogenase (ALDH) 1A in these DCs is essential for the RA production. However, it remains unclear how the steady-state ALDH1A expression is induced under specific pathogen-free (SPF) conditions. Here, we found that bone marrow-derived dendritic cells (BM-DCs) generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) expressed Aldh1a2, an isoform of Aldh1a, but that fms-related tyrosine kinase 3 ligand-generated BM-DCs did not. DCs from mesenteric lymph nodes (MLN) and Peyer's patches (PP) of normal SPF mice expressed ALDH1A2, but not the other known RA-producing enzymes. Employing a... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304157 Wed, 25 Mar 2009 04:00:00 +0100 2304157 http://www.medworm.com/index.php?rid=2304153&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F349%3Frss%3D1 The serum of patients with many autoimmune (AI) diseases contains small fractions of antibodies possessing both DNase and RNase activities. It was shown that immunization of rabbits with DNA, RNA, DNase I and RNase leads to production of antibodies with DNase and RNase activities. It is not known whether anti-idiotypic antibodies against DNase II can possess DNase or RNase activity. Electrophoretically and immunologically homogeneous polyclonal IgGs (pIgGs) from the sera of rabbits immunized with DNase II were obtained by sequential chromatography of the serum proteins on Protein A-Sepharose and gel filtration. It was shown for the first time that immunization of healthy rabbits with bovine DNase II produces IgGs with intrinsic DNase and RNase activities. IgGs from rabbits immunized with B... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304153 Wed, 25 Mar 2009 04:00:00 +0100 2304153 http://www.medworm.com/index.php?rid=2304149&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F339%3Frss%3D1 Immunological adjuvants, such as bacterial LPS, increase the mRNA levels of the IkB-related NF-B transcriptional transactivator, Bcl-3, in activated T cells. Adjuvants also increase the life expectancy of activated T cells, as does over-expression of Bcl-3, suggesting that Bcl-3 is part of the pathway whereby adjuvants affect T cell lifespans. However, previous reports, confirmed here, show that adjuvants also increase the life expectancies of Bcl-3-deficient T cells, making Bcl-3’s role and effects in adjuvant-induced survival uncertain. To investigate the functions of Bcl-3 further, here we confirm the adjuvant-induced expression of Bcl-3 mRNA and show Bcl-3 induction at the protein level. Bcl-3 was expressed in mice via a transgene driven by the human CD2 promoter. Like other prot... International Immunology journals http://www.medworm.com/rss/comments.php?id=2304149 Wed, 25 Mar 2009 04:00:00 +0100 2304149 http://www.medworm.com/index.php?rid=2304145&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F317%3Frss%3D1 The mammalian innate immune system detects the presence of microbial infection through germ line-encoded pattern recognition receptors (PRRs). Toll-like receptors, retinoic acid-inducible gene-I-like receptors and nucleotide-binding oligomerization domain-like receptors serve as PRRs that recognize different but overlapping microbial components. They are expressed in different cellular compartments such as the cell surface, endosome, lysosome or cytoplasm and activate specific signaling pathways that lead to expression of genes that tailor immune responses to particular microbes. This review summarizes recent insights into pathogen sensing by these PRRs and their signaling pathways. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2304145 Wed, 25 Mar 2009 04:00:00 +0100 2304145 http://www.medworm.com/index.php?rid=2304141&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2F313%3Frss%3D1 Innate immunity is key for host defense in a vast range of organisms, from invertebrates to vertebrates. A number of Japanese scientists have made significant contributions to the clarification of innate immune mechanisms and have applied this knowledge to treatments for various diseases including cancer, allergy and autoimmune disorders. Here, we present an overview of the development of innate immunology by highlighting several Japanese contributors. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2304141 Wed, 25 Mar 2009 04:00:00 +0100 2304141 http://www.medworm.com/index.php?rid=2304137&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F4%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2304137 Wed, 25 Mar 2009 04:00:00 +0100 2304137 http://www.medworm.com/index.php?rid=2203895&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F303%3Frss%3D1 The objective of this work was to determine the effect of treatment with the anti-Ro/SSA auto-antibodies, characterizing SS, on the expression of fibulin-6, a member of the fibulins family of the ECM, in primary human salivary gland epithelial cell (SGEC) cultures established from biopsies of labial minor salivary glands obtained from healthy donors. The induction of cell detachment and anoikis in SGECs treated with anti-Ro/SSA auto-antibodies were also investigated. Changes in fibulin-6 mRNA expression were measured by semi-quantitative reverse transcriptase-PCR and real-time PCR. Fibulin-6 expression in cells treated with anti-Ro/SSA auto-antibodies was evaluated by flow cytometric analysis and confocal laser scanning microscopy. SGECs undergoing death by anoikis were identified and quan... International Immunology journals http://www.medworm.com/rss/comments.php?id=2203895 Fri, 20 Feb 2009 05:00:00 +0100 2203895 http://www.medworm.com/index.php?rid=2203894&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F295%3Frss%3D1 In this study, we demonstrated that blocking of Delta-like (Dll) 1 alone had no significant effect on the maintenance of CD8– DCs while marginal zone (MZ) B cells were significantly reduced in the spleen of mice. On the other hand, blocking of Dll1, Dll4, Jagged1 and Jagged2 significantly decreased CD8– DCs. All these Notch ligands are expressed predominantly in the red pulp of the spleen where CD8– DCs reside. These results indicate a differential regulation of CD8– DCs and MZ B cells by Notch ligands in the spleen. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2203894 Fri, 20 Feb 2009 05:00:00 +0100 2203894 http://www.medworm.com/index.php?rid=2203893&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F283%3Frss%3D1 We examined the effect HIV has upon binding to CD4+CD25+ Treg cells by exposing human purified CD4+CD25+ T cells from healthy donors to HIV-1 in vitro and assessing their Treg-associated functional marker profile and suppressive activities. We found that HIV-1 binding increased their suppressor activities by 2- to 5-fold, which was accompanied by enhanced expression of Treg-associated functional markers sCTLA-4, glucocorticoid-induced tumor necrosis factor receptor and FoxP3. Moreover, HIV-1 binding extended the survival of CD4+CD25+ Treg cells and up-regulated the expression of homing receptors CD62L and integrin 4β7, which in turn would result in Treg cells migrating more rapidly to the peripheral lymph nodes and mucosal lymphoid tissues where anti-HIV immune responses are occurring... International Immunology journals http://www.medworm.com/rss/comments.php?id=2203893 Fri, 20 Feb 2009 05:00:00 +0100 2203893 http://www.medworm.com/index.php?rid=2203892&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F269%3Frss%3D1 In this study, we examined the differences in the potential of GM-CSF to exert tolerogenic function on CD8a+ and CD8a– sub-populations of DCs in vivo. We show that GM-CSF modulates CD8a–, but not CD8a+ DCs in vivo, by inhibiting the surface expression of activation markers MHC II and CD80 and production of inflammatory cytokines such as IL-12 and IL-1β. Self-antigen [mouse thyroglobulin (mTg)] presentation by GM-CSF-exposed CD8a– DCs to T cells from mTg-primed mice induced a profound increase in the frequency of forkhead box P3 (FoxP3)-expressing T cells compared with antigen presentation by GM-CSF-exposed CD8a+ DCs and control CD8a+ and CD8a– DCs. This tolerogenic property of GM-CD8a– DCs was abrogated when IL-12 was added. GM-CSF-exposed CD8a– DCs... International Immunology journals http://www.medworm.com/rss/comments.php?id=2203892 Fri, 20 Feb 2009 05:00:00 +0100 2203892 http://www.medworm.com/index.php?rid=2203891&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F257%3Frss%3D1 Peptides with dual binding specificity for classical HLA class I and non-classical HLA-E molecules have been identified in virus-encoded proteins, but not in cellular proteins from normal or neoplastic cells. Expression screening of a melanoma cDNA library with a CTL clone recognizing an HLA-A2-restricted tumor-specific epitope encoded by mutant peroxiredoxin 5 (Prdx5), a stress-inducible peroxidase, led to the identification of two alternatively spliced isoforms of the same gene. These isoforms, which lack the catalytic cysteine fundamental for enzymatic activity, showed widespread expression in neoplastic and normal tissues but were unstable at the protein level, being detectable, following transient transfection, only after lactacystin treatment to inhibit proteasomal degradation. Isofo... International Immunology journals http://www.medworm.com/rss/comments.php?id=2203891 Fri, 20 Feb 2009 05:00:00 +0100 2203891 http://www.medworm.com/index.php?rid=2203890&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F245%3Frss%3D1 Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in species other than Homo sapiens has been elusive, so far. Here, we provide complete phenotypic, molecular and functional characterization for NKp44 triggering receptor on Pan troglodytes NK cells, the closest human relative, and the analysis of NKp44-genomic locus and transcription in Macaca fascicularis. Similar to H. sapiens, NKp44 expression is detectable on chimpanzee NK cells only upon activation. However, basal NKp44 transcription is 5-fold higher in chimpanzees with lower differential increases upon cell activation compared with humans. Upon activation, an overall 12-fold lower NKp44 gene expression is observed in P. troglodytes compared with H. sapiens NK cells with only a slight reduction... International Immunology journals http://www.medworm.com/rss/comments.php?id=2203890 Fri, 20 Feb 2009 05:00:00 +0100 2203890 http://www.medworm.com/index.php?rid=2203889&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F237%3Frss%3D1 In conclusion, our findings confirm that DNase I is low in SLE and suggest that it may play a role in apoptosis in SLE by regulating the surface expression of the cell death molecule Fas. This role may contribute to explain the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase I to remove DNA from auto-antigenic nucleoprotein complexes. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2203889 Fri, 20 Feb 2009 05:00:00 +0100 2203889 http://www.medworm.com/index.php?rid=2203888&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F227%3Frss%3D1 Activation of T cells leads to the induction of many cytokine genes that are required for appropriate immune responses, including IL-2, a key cytokine for T cell proliferation and homeostasis. The activating transcription factors such as nuclear factor of activated T cells, nuclear factor B/Rel and activated protein-1 family members that regulate inducible IL-2 gene expression have been well documented. However, negative regulation of the IL-2 gene is less studied. Here we examine the role of zinc finger E-box-binding protein (ZEB) 1, a homeodomain/Zn finger transcription factor, as a repressor of IL-2 gene transcription. We show here that ZEB1 is expressed in non-stimulated and stimulated T cells and using chromatin immunoprecipitation assays we show that ZEB1 binds to the IL-2 promoter. ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2203888 Fri, 20 Feb 2009 05:00:00 +0100 2203888 http://www.medworm.com/index.php?rid=2203887&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F217%3Frss%3D1 In conclusion, administration of NLX as an adjuvant in combination with the gD1 DNA vaccine can enhance cell-mediated immunity and shift the immune responses to Th1. (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2203887 Fri, 20 Feb 2009 05:00:00 +0100 2203887 http://www.medworm.com/index.php?rid=2203886&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2F203%3Frss%3D1 IL-7 signaling is essential for optimal CD8 T cell function, homeostasis and establishment of memory. We have previously shown decreased expression of the IL-7 receptor -chain (CD127) on CD8 T cells from HIV-infected patients with active viral replication. We have also shown that soluble HIV Tat protein specifically down-regulates CD127 on the surface of CD8 T cells and impairs cell proliferation and cytolytic potential following stimulation with IL-7 in vitro. We now show that soluble HIV Tat protein and IL-7 at near physiologic concentrations act synergistically to suppress CD127 expression. While soluble HIV Tat protein and IL-7 both independently reduce CD127 expression on the surface of CD8 T cells, Tat concentrations of 10 µg ml–1 and IL-7 concentrations of 500 pg ml&ndas... International Immunology journals http://www.medworm.com/rss/comments.php?id=2203886 Fri, 20 Feb 2009 05:00:00 +0100 2203886 http://www.medworm.com/index.php?rid=2203885&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F3%2FNP%3Frss%3D1 (Source: International Immunology) International Immunology journals http://www.medworm.com/rss/comments.php?id=2203885 Fri, 20 Feb 2009 05:00:00 +0100 2203885 http://www.medworm.com/index.php?rid=2143846&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F2%2F187%3Frss%3D1 The immune response is regulated, in part, by effector cells whose activation requires multiple signals. For example, T cells require signals emanating from the T cell antigen receptor and co-stimulatory molecules for full activation. Here, we present evidence indicating that IgE-mediated hypersensitivity reactions in vivo also require cognate signals to activate mast cells. Immediate hypersensitivity reactions in the conjunctiva are ablated in mice deficient in eotaxin-1, despite normal numbers of tissue mast cells and levels of IgE. To further define the co-stimulatory signals mediated by chemokine receptor 3 (CCR3), an eotaxin-1 receptor, effects of CCR3 blockade were tested with an allergic conjunctivitis model and in ex vivo isolated connective tissue-type mast cells. Our results show... International Immunology journals http://www.medworm.com/rss/comments.php?id=2143846 Thu, 29 Jan 2009 05:00:00 +0100 2143846 http://www.medworm.com/index.php?rid=2143845&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F2%2F179%3Frss%3D1 In this study, the potential to produce immunoregulatory cytokines by these cells was characterized in order to find the mechanism underlying their immunoregulatory functions. Serum levels of IL-4, IL-10, transforming growth factor-β, IFN- and IL-17 increased in mice over-expressing an invariant V19-J33 TCR transgene (V19 Tg) in response to anti-CD3 antibody injection. NK1.1+ V19 Tg+, but not NK1.1– V19 Tg+ cells, promptly produced immunoregulatory IL-4, IFN- and IL-17 upon invariant TCR engagement with immobilized anti-CD3 antibody in culture. The activation of V19 Tg+ cells then triggered the production of pro-inflammatory cytokines by bystander cells. Interestingly, the ratio of Th2 cytokines such as IL-4, IL-5 and IL-10, but not pro-inflammatory IL-17, to IFN- was increased ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2143845 Thu, 29 Jan 2009 05:00:00 +0100 2143845 http://www.medworm.com/index.php?rid=2143844&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F2%2F167%3Frss%3D1 CD47 is a ubiquitously expressed molecule which has been attributed a role in many cellular processes. Its role in preventing cellular phagocytosis has defined CD47 as an obligatory self-molecule providing a ‘don't-eat-me-signal’. Additionally, CD47–CD172a interactions are important for cellular trafficking. Yet, the contribution of CD47 to T cell stimulation remains controversial, acting sometimes as a co-stimulator and sometimes as an inhibitor of TCR signalling or peripheral T cell responses. Most of the experiments leading to this controversy have been carried in in vitro systems. Moreover, the role of CD47 on thymocyte differentiation, which precisely relies on TCR signal strength, has not been evaluated. Here, we examine the in vivo role of CD47 in T cell differenti... International Immunology journals http://www.medworm.com/rss/comments.php?id=2143844 Thu, 29 Jan 2009 05:00:00 +0100 2143844 http://www.medworm.com/index.php?rid=2143843&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F2%2F155%3Frss%3D1 We examined whether positron emission tomography (PET) can monitor the distribution of self-antigen-specific T cells engineered to express an herpes simplex virus 1 thymidine kinase (sr39tk) PET reporter gene. Micro-PET imaging using the sr39tk-specific substrate 9-[4-[18F]fluoro-3-(hydroxymethyl)-butyl]guanine ([18F]FHBG) enabled the detection of transplanted T cells in secondary lymphoid organs of recipient mice over a 3-week period. Tumor responses could be predicted as early as 3 days following AT when a >25-fold increase of micro-PET signal in the spleen and 2-fold increase in lymph nodes (LNs) were observed in mice receiving combined immunotherapy versus control mice. The lower limit of detection was ~7 x 105 T cells in the spleen and 1 x 104 T cells in LNs. Quantification of tran... International Immunology journals http://www.medworm.com/rss/comments.php?id=2143843 Thu, 29 Jan 2009 05:00:00 +0100 2143843 http://www.medworm.com/index.php?rid=2143842&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F2%2F145%3Frss%3D1 NK and NK-like T cells play an essential role in linking innate and adaptive immunity through their ability to secrete IFN-. The exact trigger initiating production of IFN- is uncertain. Antigen-presenting cell (APC)-derived IL-12 is thought to be the classical IFN--inducing cytokine but requires an additional stimulus such as IFN- itself. IL-23 and IL-18 are among the first cytokines secreted by APC in response to binding of pathogen-associated molecular patterns such as LPS. Thus, early APC-derived IL-23 may be an initial trigger of IFN- production in NK and NK-like T cells. Herein, we characterized the effect of IL-23 on IFN- secretion by NK and NK-like T cells. Our findings show that IL-23 and IL-18 synergistically elicit IFN- production in NK-like T cells but not in NK cells. In contr... International Immunology journals http://www.medworm.com/rss/comments.php?id=2143842 Thu, 29 Jan 2009 05:00:00 +0100 2143842 http://www.medworm.com/index.php?rid=2143841&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F2%2F137%3Frss%3D1 Toward obtaining a more comprehensive understanding of factors governing activation and/or function during visceral leishmaniasis (VL), we have compared active disease (pre-treatment) versus post-chemotherapy immune response in VL patients by means of ex vivo staining with different cell markers. Our results show that during active disease, the frequency of T cells positive for CD25, CTLA-4 and CD45RO was significantly lower in VL patients compared with healthy controls, whereas cells staining positive for Annexin V and CD95 were significantly higher. In all cases, chemotherapy was able to restore these frequencies to normal levels. Interestingly, significant differences in the frequency of CD18 and in the frequency of CD45RO-positive cells were observed in the CD8+ T cell subset. These tw... International Immunology journals http://www.medworm.com/rss/comments.php?id=2143841 Thu, 29 Jan 2009 05:00:00 +0100 2143841 http://www.medworm.com/index.php?rid=2143840&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F2%2F123%3Frss%3D1 It has been shown previously that CD8β in vitro increases the range and the sensitivity of antigen recognition and in vivo plays an important role in the thymic selection of CD8+ T cells. Consistent with this, we report here that CD8+ T cells from CD8β knockout (KO) P14 TCR transgenic mice proliferate inefficiently in vitro. In contrast to these findings, we also show that CD8β KO mice mount normal CD8 primary, secondary and memory responses to acute infection with lymphocytic choriomeningitis virus. Tetramer staining and cytotoxic experiments revealed a predominance of CD8-independent CTL in CD8β KO mice. The TCR repertoire, especially the one of the TCR chain, was different in CD8β KO mice as compared with B6 mice. Our results indicate that in the absence of CD8&... International Immunology journals http://www.medworm.com/rss/comments.php?id=2143840 Thu, 29 Jan 2009 05:00:00 +0100 2143840 http://www.medworm.com/index.php?rid=2143839&cid=s_33157_3_f&fid=33157&url=http%3A%2F%2Fintimm.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F21%2F2%2F113%3Frss%3D1 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] and the vitamin D receptor (VDR) are important regulators of autoimmunity. The effect of the VDR on the ability of mice to fight a primary or secondary infection has not been determined. Young and old VDR knockout (KO) mice were able to clear both primary and secondary infections with Listeria monocytogenes. However, the kinetics of clearance was somewhat delayed in the absence of the VDR. Memory T cell development was not different in young VDR KO and wild-type (WT) mice; however, old VDR KO mice had significantly less memory T cells than their WT counterparts but still mounted an adequate immune response as determined by the complete clearance of L. monocytogenes. Although the primary and secondary immune responses were largely intact in the VDR KO ... International Immunology journals http://www.medworm.com/rss/comments.php?id=2143839 Thu, 29 Jan 2009 05:00:00 +0100 2143839