Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Injection of mercuric chloride into Brown Norway (BN) rats induces a T lymphocyte-dependent autoimmune syndrome. In order to investigate whether modification of adhesion and costimulatory molecules on T lymphocytes may be involved in early T lymphocyte activation by HgCl2, the authors analysed expression of these molecules in peripheral lymph node cells from BN rats at day 4 after injection of HgCl2. Tri-colour flow cytometry was performed for expression analysis within CD45RC-defined subsets of CD4+ and CD8+ cells. Compared to control rats, HgCl2-exposed rats showed increased numbers of lymphocytes, especially of T lymphocyte blast cells. The levels of LFA-1 expression as well as the fractions of ICAM-1 + cells were significantly increased in all CD45RC-defined subsets of CD4+ and CD8+ cells. Within the CD4 + CD45RC10 T lymphocyte population, HgCl2-injected rats showed a highly significant increase in the number of cells expressing OX40, which is a member of the TNF receptor family. Moreover, only CD4 + CD45RC10 blast cells of HgCl2-exposed rats showed decreased expression of CD43, increased expression of CD49d and decreased numbers of CD26 + cells. The results indicate that induction of autoimmunity by HgCl2 in BN rats is associated with altered expression of T lymphocyte costimulatory molecules, predominantly on CD4+ CD45RC10 cells, which may be caused by a direct effect of HgCl2 on these cells, and may precipitate further activation of T and B lymphocytes by HgCl2.
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PMID:Enhanced T lymphocyte expression of LFA-1, ICAM-1, and the TNF receptor family member OX40 in HgCl2-induced systemic autoimmunity. 863 8

Exposure of Brown Norway (BN) rats to HgCl2 induces Th2-mediated systemic autoimmunity. In contrast, in Lewis rats, HgCl2 induces immune suppression, mediated by CD8+ T cells. HgCl2 was previously found to enhance expression of LFA-1, ICAM-1 and CD134 (OX40) on T cells in BN rats. In the present study, T cells from Lewis rats were studied at day 4 after injection of HgCl2. CD8+ T lymphoblasts were significantly increased, which were predominantly CD45RC(hi), and which showed enhanced LFA-1 expression. Furthermore, CD4+CD45RC(hi) T cells showed increased numbers of ICAM-1+ cells, whereas expression of CD134 and CD26 was relatively decreased in CD4+ T lymphoblasts. Ex vivo experiments demonstrated that HgCl2-exposure of BN rats, but not of Lewis rats, significantly enhances PMA [phorbol 12-myristate 13-acetate]-induced lymphocyte aggregation, mediated by LFA-1 and ICAM-1. In conclusion, HgCl2-injected Lewis rats show early signs of T-lymphocyte activation, predominantly on CD8+ cells. Strain-dependent effects of HgCl2 on cell adhesion molecules and expression of CD134 may play an important role in development of either autoimmunity or immune suppression.
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PMID:Differential expression of T-cell adhesion molecules and LFA-1-dependent intercellular adhesion in HgCl2-induced autoimmunity and immune suppression. 979 Mar 9

Intravenous immunoglobulin (IVIg) was shown to decrease the severity of acute graft-versus-host disease (aGVHD) in recipients of allogeneic bone marrow transplants. To investigate the mechanisms involved in the protective effect of IVIg, we have used the parent-into-F1 model in which parental lymphocytes are transferred into semi-syngeneic non-irradiated F1 rats. Here we report that IVIg, as well as F(ab')(2) fragments of IVIg, protected (Lewis x Brown-Norway) F1 rats against aGVHD induced by a single injection of Lewis lymphocytes. IVIg was given as five consecutive daily injections, starting on the day preceding that of the transfer of Lewis cells. Protection was associated with a decreased ability of lymphocytes to spontaneously proliferate and to produce NO and IFN-gamma, in the absence of an increased production of IL-10. We further demonstrate that protection was associated with a decrease in CD4(+) T cells bearing the activation marker CD134 in vivo, and with an enhanced apoptosis of activated CD4(+) T cells by IVIg, in vitro. Our observations suggest that the prevention of aGVHD by IVIg in this model is mediated by the induction of apoptosis of activated alloreactive CD4(+)CD134(+) donor T cells. The results further emphasize the role of normal immunoglobulin in modulating alloantigen immune responsiveness.
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PMID:Normal IgG protects against acute graft-versus-host disease by targeting CD4(+)CD134(+) donor alloreactive T cells. 1153 77

Mercuric chloride (HgCl2)-induced autoimmunity in Brown Norway rats is a spontaneously resolving autoimmune response driven by the activation of T helper type 2 lymphocytes (Th2 cells). Treatment with antibody to OX40-ligand (OX40-L) from the time of the first HgCl2 injection for 12 days had little effect. Delayed treatment commenced 8 days after the first HgCl2 injection significantly suppressed immunoglobulin E production, splenomegaly, weight loss and mortality. This makes OX40/OX40-L signalling an attractive therapeutic target for Th2-driven autoimmune diseases. Intravenous administration of the murine antibody to OX-40-L elicited a vigorous anti-mouse immunoglobulin antibody response that was significantly enhanced compared to the response to control immunoglobulin. It is likely that this response significantly reduced the plasma half-life of the anti-OX40-L antibody and this observation has clear implications for the interpretation of data from experiments where anti-OX40-L is used in vivo.
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PMID:Blockade of OX40-ligand after initial triggering of the T helper 2 response inhibits mercuric chloride-induced autoimmunity. 1647 60