Search results for "MHC class II"
showing 10 items of 82 documents
Structure Learning in Nested Effects Models
2007
Nested Effects Models (NEMs) are a class of graphical models introduced to analyze the results of gene perturbation screens. NEMs explore noisy subset relations between the high-dimensional outputs of phenotyping studies, e.g., the effects showing in gene expression profiles or as morphological features of the perturbed cell. In this paper we expand the statistical basis of NEMs in four directions. First, we derive a new formula for the likelihood function of a NEM, which generalizes previous results for binary data. Second, we prove model identifiability under mild assumptions. Third, we show that the new formulation of the likelihood allows efficiency in traversing model space. Fourth, we…
Neuronal nitric oxide synthase modulates maturation of human dendritic cells.
2010
AbstractDendritic cells (DCs) are the most potent APCs of the immune system. Understanding the intercellular and intracellular signaling processes that lead to DC maturation is critical for determining how these cells initiate T cell-mediated immune processes. NO synthesized by the inducible NO synthase (iNOS) is important for the function of murine DCs. In our study, we investigated the regulation of the arginine/NO-system in human monocyte-derived DCs. Maturation of DCs induced by inflammatory cytokines (IL-1β, TNF, IL-6, and PGE2) resulted in a pronounced expression of neuronal NOS (nNOS) but only minimal levels of iNOS and endothelial NOS were detected in human mature DCs. In addition, …
Cortical neurons selectively inhibit MHC class II induction in astrocytes but not in microglial cells.
1993
Astrocytes have been shown to act as potent accessory cells for MHC class II-restricted T cell responses in vitro after treatment with interferon-gamma. In contrast, even under conditions of severe central nervous system (CNS) inflammation, they seem to express little, if any, class II molecules in vivo. Thus the role of astroglial cells as accessory cells in immune responses in the CNS remains to be determined. We have studied neuron--glia interactions with respect to induction of MHC class II molecules. Surprisingly, in a co-culture system, viable neurons inhibited the induction of class II restriction elements on astrocytes. This effect was only observed when neurons had contact to astro…
Macrophages are dispensable for superantigen-mediated stimulation and anergy induction of peripheral T cells in vivo.
1994
Bacterial superantigens provoke T lymphocyte activation by cross-linking the variable part of the T cell receptor (TCR) beta-chain with MHC class II molecules on antigen-presenting cells. Although the molecular mechanisms of this interaction are well characterized, the in vivo accessory cell requirements for this stimulation of T lymphocytes by bacterial superantigens remain unknown. In the present study we have addressed the role of splenic macrophages in the activation of V beta 8+ peripheral T cells by staphylococcal enterotoxin B (SEB) in BALB/c mice. SEB-triggered clonal expansion and subsequent induction of unresponsiveness of both CD4+ and CD8+ T cells were investigated in naive anim…
Thymoma and paraneoplastic myasthenia gravis
2010
Paraneoplastic autoimmune diseases associate occasionally with small cell lung cancers and gynecologic tumors. However, myasthenia gravis (MG) occurs in at least 30% of all patients with thymomas (usually present at MG diagnosis). These epithelial neoplasms almost always have numerous admixed maturing polyclonal T cells (thymocytes). This thymopoiesis-and export of mature CD4(+)T cells-particularly associates with MG, though there are rare/puzzling exceptions in apparently pure epithelial WHO type A thymomas. Other features potentially leading to inefficient self-tolerance induction include defective epithelial expression of the autoimmune regulator (AIRE) gene and/or of major histocompatib…
Release of dendritic cells from cognate CD4 + T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimm…
2012
Resting dendritic cells (DCs) induce tolerance of peripheral T cells that have escaped thymic negative selection and thus contribute significantly to protection against autoimmunity. We recently showed that CD4 + Foxp3 + regulatory T cells (Tregs) are important for maintaining the steady-state phenotype of DCs and their tolerizing capacity in vivo. We now provide evidence that DC activation in the absence of Tregs is a direct consequence of missing DC–Treg interactions rather than being secondary to generalized autoimmunity in Treg-less mice. We show that DCs that lack MHC class II and thus cannot make cognate interactions with CD4 + T cells are completely unable to induce peripheral CD8 +…
Analysis of Invariant Chain Processing in 3 Day Cultured Rat Langerhans Cells
1995
MHC class II molecules, critical peptide binding elements involved in the presentation of exogenous antigen to T helper cells, are expressed constitutively by Langerhans cells (LC) within their epidermal microenvironment. Several studies in mouse and man demonstrated, that short term in vitro culture of LC entails remarkable functional and penotypic alterations, including a profound increase of class II elements exposed at the LC’s surface1. Biosynthetic analysis revealed a downregulation of class II synthesis during the culture period2,3. In recent work on rat LC we described the uncoupling of the coordinately regulated biosynthesis of class II and invariant chain proteins in the course of…
Granulocyte-macrophage colony-stimulating factor-cultured bone marrow-derived macrophages reveal accessory cell function and synthesis of MHC class I…
1988
The antigen-mediated activation of a number of T cell clones by bone marrow (BM) cells cultivated in the presence of various colony-stimulating factor (CSF) preparations was investigated. BM macrophages (BMM phi) grown in L929 cell supernatant as a crude source of macrophage colony-stimulating factor (M-CSF) as well as BM cells propagated in the presence of recombinant M-CSF exhibited transient antigen presentation potential to some T cell clones, being maximal on day 7 and having declined to a low level by day 19 of in vitro culture. Treatment of these long-term-cultivated BMM phi populations with recombinant interferon-gamma (IFN-gamma) resulted in predominant antigen presentation capacit…
Induction of dendritic cell maturation and modulation of dendritic cell-induced immune responses by prostaglandins
2000
Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system. In this study we investigated the effects of various prostaglandins (PG) on the stimulatory capacity of DC. DC were generated from peripheral progenitor cells in the presence of IL-4 and GM-CSF and stimulated with IL-1, IL-6 and TNF-alpha on day 7. Simultaneously, PG (PGD(2), PGE(1), PGE(2), PGF(2 alpha), PGI(2)) were added at various concentrations (10(-5) to 10(-9) M) on day 7. In all experiments, PGE(2) had the most potent influence on the maturation of the DC, followed by other PG in the order PGE(1) > PGD(2) > PGF(2 alpha) > PGI(2). In addition, the expression of the surface molecules CD40, CD54, CD…
Analysis of HLA-DRB1,DQA1,DQB1 haplotypes in Sardinian centenarians
2008
Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a ro…