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MHC II (mhc + ii)
Selected AbstractsCross-Primed CD8+ Cytotoxic T cells Induce Severe Helicobacter -associated Gastritis in the Absence of CD4+ T cellsHELICOBACTER, Issue 5 2007Toshiro Fukui Abstract Background:, Although previous studies have reported important roles of CD4+ type1-helper T cells and regulatory T cells in Helicobacter -associated gastritis, the significance of CD8+ cytotoxic T cells remains unknown. To study the roles of CD8+ T cells, we examined the immune response in the gastric mucosa of Helicobacter felis -infected major histocompatibility complex (MHC) class II-deficient (II,/,) mice, which lack CD4+ T cells. Materials and methods:, Stomachs from H. felis -infected wild-type and infected MHC II,/, mice were examined histologically and immunohistochemically. Gastric acidity and serum levels of anti- H. felis antibodies were measured. The expression of pro-inflammatory and anti-inflammatory cytokine, Fas-ligand, perforin, and Foxp3 genes in the gastric mucosa was investigated. Results:,H. felis -infected MHC II,/, mice developed severe gastritis, accompanied by marked infiltration of CD8+ cells. At 1 and 2 months after inoculation, mucosal inflammation and atrophy were more severe in MHC II,/, mice, although gastritis had reached similar advanced stages at 3 months after inoculation. There was little infiltration of CD4+ cells, and no Foxp3 -positive cells were detected in the gastric mucosa of the infected MHC II,/, mice. The expression of the interleukin-1, and Fas-ligand genes was up regulated, but that of Foxp3 was down regulated in the infected MHC II,/, mice. Serum levels of anti- H. felis antibodies were lower in the infected MHC II,/, mice, despite severe gastritis. Conclusions:, The present study suggests that cross-primed CD8+ cytotoxic T cells can induce severe H. -associated gastritis in the absence of CD4+ helper T cells and that Foxp3 -positive cells may have an important role in the control of gastric inflammation. [source] Mechanism of T cell tolerance induction by murine hepatic Kupffer cells,HEPATOLOGY, Issue 3 2008Qiang You The liver is known to favor the induction of immunological tolerance rather than immunity. Although Kupffer cells (KC) have been indicated to play a role in liver tolerance to allografts and soluble antigens, the mechanisms involved remain unclear. We hypothesized that KCs could promote immune tolerance by acting as incompetent antigen-presenting cells (APC), as well as actively suppressing T cell activation induced by other potent APCs. The expression of antigen presentation-related molecules by KCs was phenotyped by flow cytometry. The abilities of KCs to act as APCs and to suppress T cell activation induced by splenic dendritic cells (DC) were examined by in vitro proliferation assays using CD4+ OVA-TCR (ovalbumin T cell receptor) transgenic T cells. We found that, compared with DCs, KCs expressed significantly lower levels of major histocompatibility complex (MHC) II, B7-1, B7-2, and CD40. This result is consistent with our observation that KCs were not as potent as DCs in eliciting OVA-specific T cell proliferation. However, KCs isolated from polyinosinic:polycytidylic acid,treated mice expressed significantly higher levels of MHC II and costimulatory molecules than did naïve KCs and could stimulate stronger T cell responses. More importantly, we found that KCs could inhibit DC-induced OVA-specific T cell activation. Further investigation of the underlying mechanism revealed that prostaglandins produced by KCs played an important role. The results ruled out the possible involvement of interleukin-10, nitric oxide, 2,3-dioxygenase, and transforming growth factor , in KC-mediated T cell suppression. Conclusion: Our data indicate that KCs are a tolerogenic APC population within the liver. These findings suggest that KCs may play a critical role in regulating immune reactions within the liver and contributing to liver-mediated systemic immune tolerance. (HEPATOLOGY 2008.) [source] The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanismsIMMUNOLOGICAL REVIEWS, Issue 1 2004John P. Cannon Summary:, The adaptive immune system arose in ancestors of the jawed vertebrates approximately 500 million years ago. Homologs of immunoglobulins (Igs), T-cell antigen receptors (TCRs), major histocompatibility complex I (MHC I) and MHC II, and the recombination-activating genes (RAGs) have been identified in all extant classes of jawed vertebrates; however, no definitive homolog of any of these genes has been identified in jawless vertebrates or invertebrates. RAG-mediated recombination and associated junctional diversification of both Ig and TCR genes occurs in all jawed vertebrates. In the case of Igs, somatic variation is expanded further through class switching, gene conversion, and somatic hypermutation. Although the identity of the ,primordial' receptor that was interrupted by the recombination mechanism in jawed vertebrates may never be established, many different families of genes that exhibit predicted characteristics of such a receptor have been described both within and outside the jawed vertebrates. Recent data from various model systems point toward a continuum of immune receptor diversity, encompassing many different families of recognition molecules whose functions are integrated in an organism's response to pathogenic invasion. Various approaches, including both genomic and protein-functional analyses, currently are being applied in jawless vertebrates, protochordates, and other invertebrate deuterostome systems and may yield definitive evidence regarding the presence or absence of adaptive immune homologs in species lacking adaptive immune systems. Such studies have the potential for uncovering previously unknown mechanisms of generating receptor diversity. [source] Major histocompatibility complex (MHC) class II but not MHC class I molecules are required for efficient control of Strongyloides venezuelensis infection in miceIMMUNOLOGY, Issue 1pt2 2009Rosângela M. Rodrigues Summary Strongyloides stercoralis is an intestinal nematode capable of chronic, persistent infection and hyperinfection of the host; this can lead to dissemination, mainly in immunosuppressive states, in which the infection can become severe and result in the death of the host. In this study, we investigated the immune response against Strongyloides venezuelensis infection in major histocompatibility complex (MHC) class I or class II deficient mice. We found that MHC II,/, animals were more susceptible to S. venezuelensis infection as a result of the presence of an elevated number of eggs in the faeces and a delay in the elimination of adult worms compared with wild-type (WT) and MHC I,/, mice. Histopathological analysis revealed that MHC II,/, mice had a mild inflammatory infiltration in the small intestine with a reduction in tissue eosinophilia. These mice also presented a significantly lower frequency of eosinophils and mononuclear cells in the blood, together with reduced T helper type 2 (Th2) cytokines in small intestine homogenates and sera compared with WT and MHC I,/, animals. Additionally, levels of parasite-specific immunoglobulin M (IgM), IgA, IgE, total IgG and IgG1 were also significantly reduced in the sera of MHC II,/, infected mice, while a non-significant increase in the level of IgG2a was found in comparison to WT or MHC I,/, infected mice. Together, these data demonstrate that expression of MHC class II but not class I molecules is required to induce a predominantly Th2 response and to achieve efficient control of S. venezuelensis infection in mice. [source] Binding interactions between peptides and proteins of the class II Major Histocompatibility ComplexMEDICINAL RESEARCH REVIEWS, Issue 2 2002Benjamin J. McFarland Abstract The activation of helper T cells by peptides bound to proteins of the class II Major Histocompatibility Complex (MHC II) is pivotal to the initiation of an immune response. The primary functional requirement imposed on MHC II proteins is the ability to efficiently bind thousands of different peptides. Structurally, this is reflected in a unique architecture of binding interactions. The peptide is bound in an extended conformation within a groove on the membrane distal surface of the protein that is lined with several pockets that can accommodate peptide side-chains. Conserved MHC II protein residues also form hydrogen bonds along the length of the peptide main-chain. Here we review recent advances in the study of peptide-MHC II protein reactions that have led to an enhanced understanding of binding energetics. These results demonstrate that peptide-MHC II protein complexes achieve high affinity binding from the array of hydrogen bonds that are energetically segregated from the pocket interactions, which can then add to an intrinsic hydrogen bond-mediated affinity. Thus, MHC II proteins are unlike antibodies, which utilize cooperativity among binding interactions to achieve high affinity and specificity. The significance of these observations is discussed within the context of possible mechanisms for the HLA-DM protein that regulates peptide presentation in vivo and the design of non-peptide molecules that can bind MHC II proteins and act as vaccines or immune modulators. © 2002 John Wiley & Sons, Inc. Med Res Rev, 22, No. 2, 168,203, 2002; DOI 10.1002/med.10006 [source] Antibody blocking of MHC II on human activated regulatory T cells abrogates their suppressive potentialALLERGY, Issue 7 2007M. Peiser Natural regulatory CD4+CD25+Foxp3+ T cells control peripheral immune responses. Freshly isolated regulatory T-cell populations are regarded as being unable to suppress the proliferation of strongly stimulated effector T cells. We now provide evidence that it is not the strength of the proliferative signal to effector T cells but activation and accessibility of regulatory T cells that determine whether suppression may occur. Human regulatory T cells were initially cocultured with allogeneic monocyte-derived dendritic cells for a short time and were then rendered accessible for effector T cells by removal of the dendritic cells. That way activated regulatory T cells effectively suppressed the proliferation of autologous effector T cells which was strongly driven by cell-sized Dynabeads coated with CD3/CD28 antibodies. Although regulatory T cells are known to display MHC II molecules and to upregulate their expression along with activation, a role of MHC II molecules in forming the contact to effector T cells was not yet envisaged. However, blocking of MHC II on activated regulatory T cells abrogated their suppressive potential. It should not be excluded that self-MHC molecules on physically accessible activated regulatory T cells arrange the contact to effector T cells. [source] Effect of renal and non-renal ischemia/reperfusion on cell-mediated immunity in organs and plasmaAPMIS, Issue 2 2010ANNE C. BRØCHNER Brøchner AC, Dagnæs-Hansen F, Toft P. Effect of renal and non-renal ischemia/reperfusion on cell-mediated immunity in organs and plasma. APMIS 2010; 118: 101,7. Acute renal failure (ARF) is a common morbidity factor among patients in the intensive care unit, reaching an incidence from 3% to 30% depending on the definition of ARF and the population. Although the majority of the patients with ARF are treated with continuous renal replacement therapy, the mortality rate still remains above 50%. The causes of death are primarily extra-renal and include infection, shock, septicemia, and respiratory failure. We wanted to evaluate the cell-mediated inflammatory response of renal ischemia,reperfusion (I/R) and non-renal I/R, in blood and in distant organs. In our study, 80 mice were divided into four groups. The following surgeries were performed on the groups compared: bilateral renal I/R by clamping, unilateral renal ischemia, anesthesia only, and unilateral hind leg I/R. Half of the animals were killed after 2 h and the other half after 24 h. To assess the inflammatory response, we measured myeloperoxidase (MPO) in the organs, and CD 11b and major histocompatibility complex (MHC) II-positive cells in the blood. Non-renal I/R elicited the most elevated levels of MPO in extra-renal tissue such as the lungs. There was a trend toward higher MPO levels in the kidney following renal I/R. All kinds of I/R induced an upregulation of the adhesion molecule CD 11b and a downregulation of MHC II. Renal and non-renal I/R induced neutrophil infiltration in distant organs. Renal I/R does not induce a larger cell-mediated inflammatory response in blood and organs than non-renal I/R. [source] Immune response of DNA vaccine against lymphocystis disease virus and expression analysis of immune-related genes after vaccinationAQUACULTURE RESEARCH, Issue 10 2010Feng Rong Zheng Abstract In this study, we found that an intramuscular injection of Japanese flounder (Paralichthys olivaceus, 60,80 g in weight and 15,20 mL in length) with 5 ,g of a DNA vaccine (pEGFP-N2-LCDV-cn-MCP 0.6 kb, containing lymphocystis disease virus major capsid protein gene) induced a strong immune response. Subsequent real-time polymerase chain reaction showed that the expression of immune-related genes [e.g., major histocompatibility complex (MHC) class I ,, MHC II ,, T-cell receptor (TCR), tumour necrosis factor (TNF), tumour necrosis factor receptor (TNFR), Mx, interleukin (IL)-1,, CXC and IL-8R] was significantly changed after DNA vaccination. The most remarkable alternation was the expression of MHC I , and MHC II , genes: MHC II , reached the maximum on day 8 in different tissues, and MHC I , on day 2 in the intestine and gills. The expression of TCR increased and reached a plateau in 2 days in the spleen, gills, kidney and liver after vaccination and then decreased after day 8. In contrast, the expression of TCR in the intestine increased and reached a plateau in 8 days. The expression of IL-8R reached the maximum on day 2 in different tissues and then decreased on day 8. Mx increased in the gills, kidney, spleen and liver on days 2, 8, 2 and 2, but decreased in the intestine, gills, spleen and liver on days 2, 8, 8 and 8 respectively. The TNFR expression increased in the spleen, kidney and gills on days 2, 8 and 8, but decreased in intestine, liver and gills on days 2, 8 and 8 respectively. The expression of TNF, CXC and IL-1, increased 2 and 8 days after the injection of DNA vaccine. However, the expression of TNF, CXC and IL-1, altered on days 2 and 8 with different patterns in different tissues respectively. The fish responded to the DNA vaccine by yielding a specific immunoglobulin against lymphocystis disease virus (LCDV) as observed with indirect ELISA. The DNA vaccine induced a unique humoral response, suggesting that the DNA vaccine activated both cellular and humoral defences of the specific immune system of Japanese flounder. [source] Upregulation of Group 1 CD1 Antigen Presenting Molecules in Guinea Pigs with Experimental Autoimmune Encephalomyelitis: An Immunohistochemical StudyBRAIN PATHOLOGY, Issue 1 2003Barbara Cipriani In humans, group 1 CD1 glycoproteins present foreign and self lipid and glycolipid antigens to Tcells. Homologues of these molecules are not found in mice or rats but are present in guinea pigs (GPs). We examined CD1 and MHC class II expression in the central nervous system (CNS) of GPs sensitized for experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. In normal GPs and the uninflamed CNS, low-level MHC class II (MHC II) immunoreactivity occurred on vascular elements, meningeal macrophages and parenchymal microglial cells, whereas immunoreactivity for CD1 was absent. In the inflamed CNS, the majority of infiltrating cells were MHC II+ and microglia showed increased expression. CD1 immunoreactivity was detected on astrocytes and subsets of inflammatory cells including B cells and macrophages. Minimal CD1 and MHC II co-expression was noted on inflammatory cells or glia. We conclude that group 1 CD1 molecules are strongly upregulated in the inflamed CNS on subsets of cells distinct from the majority of MHC II bearing cells. The expression of CD1 proteins in such lesions broadens the potential repertoire of antigens recognized at these sites and highlights the value of the GP as a model for studies of the relevance of CD1 molecules in host defense and autoimmune diseases. [source] Gene transfer of disease regulated promoters during experimental autoimmune uveitisACTA OPHTHALMOLOGICA, Issue 2009V ELMALEH Purpose Adeno-associated virus (AAV) vectors have been successfully used to transfer immunosuppressive genes into the retina to prevent experimental uveitis development. Transgene expression is classically regulated by constitutive or tetracycline inducible promoters. It might be more advantageous that the control of transgene expression depends on the pathological process itself. Inflammation activates transcription factors acting on promoters containing short responsive sequences, responding, for example to nuclear factor kappa B (NF,B-RE). These responsive elements can be used to generate disease regulated promoters. Methods An AAV vector with the GFP gene under the control of a NF-kB-RE containing promoter will be injected subretinally in C57Bl6 mice. Autoimmune uveitis will be induced by adoptive transfer of IRBP specific lymphocytes. Animals will be sacrificed at different time points. GFP expression will be analysed by immunofluorescence. VCAM1, MHC II and CD45 will be analysed by immunofluorescence and used to monitor the level of retinal inflammation. Results One week after disease induction, GFP expression was found in eyes injected with this new vector. Milder GFP expression was also found in mice who did not received adoptive transfer. This background was increased a J14. Conclusion Our preliminary results suggest that disease driven GFP expression can be obtained by the use of AAV vectors containing disease regulated promoters. We still need some more times to improve our model. In the future, we plan to replace the GFP gene by an immunosuppressive gene and test if the system can be use to treat experimental uveitis. [source] | ||||||||||