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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemically induced autoimmunity is a recently recognized environmental hazard that may affect individuals genetically predisposed to autoimmune disease and chronically exposed to certain chemicals. For example, moderate concentrations of mercury may lead to renal autoimmune disease in a small but significant percentage of the exposed population. Mercury also induces autoimmune glomerulonephritis in susceptible Brown Norway (BN) and MAXX inbred strain rats. Autoimmune responses, directed to epitopes of the renal glomerular basement membrane (GBM), are rapid in onset and have a self-limiting course in mercury-treated rats. Both regulatory T cells and idiotype-anti-idiotype network have been implicated in the resolution of this autoimmune process. In our investigations of immune regulation of mercury-induced autoimmune glomerulonephritis, we have used flow cytometry to quantitate lymphocyte subpopulations in the spleen and lymph nodes of mercury-treated and control BN rats. Of particular interest was the RT6+ T cell subset, that appears to have important immunoregulatory properties in a rat model of autoimmune insulin-dependent diabetes mellitus. Spleen and lymph nodes from control BN rats contained 22 and 52%, respectively, RT6+ cells. Spleens from mercury-treated animals contained 21% RT6+ cells on Day 10 of treatment, 13% on Day 17, 16% on Day 24 and 20% on Day 30. Lymph nodes from the same rats had 36% RT6+ cells on Day 10, 23% on Day 17, 29% on Day 24, and 28% on Day 30. The decrease in RT6+ cells correlated inversely with autoimmune responses to GBM, which peaked on Days 17-24 and declined by Day 30. Moreover, autoimmune responses were also associated with elevated RT6-:RT6+ T cell ratios. Similar results were obtained in two additional groups of BN rats, comprising both younger and older animals, sacrificed at Day 18 of mercury treatment. Analysis of other lymphocyte subpopulations demonstrated a decrease of CD4+ and CD5+ cells, whereas B cells as well as CD8+, IL-2 receptor+, and MHC class II+ subsets showed no consistent correlation with the onset or resolution of the autoimmune process. These findings suggest that mercury-induced changes in RT6+ T lymphocytes may be related to the development of renal autoimmune disease in genetically predisposed BN rats.
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PMID:Reduction of the RT6.2+ subset of T lymphocytes in brown Norway rats with mercury-induced renal autoimmunity. 201 77

Brown Norway (BN) rats, "susceptible" to the autoimmune effects of mercury, experience a decrease of peripheral RT6.2+ T lymphocytes after the injection of relatively low doses of mercuric chloride. This change coincides with the appearance of circulating autoantibodies to renal antigens (e.g., laminin). Lewis (LEW) rats, "resistant" to the autoimmune effects of mercury, do not show significant decreases of RT6+ T cells. It is possible that BN rats are particularly sensitive to stress induced by mercury and that secretion of adrenocortical hormones decreases levels of RT6+ T cells in this rat strain. Alternatively, mercury may induce a graft-versus-host-like syndrome in BN rats, resulting in higher levels of corticosteroids capable of affecting RT6+ lymphocytes. To eliminate the possible influence of adrenocortical hormones, we have adrenalectomized BN rats prior to administration of mercury. Autoimmune responses to renal antigens were not affected by this experimental manipulation. Similarly, adrenalectomized rats exposed to mercury showed a significant decrease of RT6+ T lymphocytes in cervical lymph nodes. Overall, these observations do not support the hypothesis that increases in adrenocortical hormones play a major role in mercury-induced changes of RT6+ T cells. We have also explored whether experimental depletion of RT6+ T lymphocytes would result in autoimmunity. Gamma irradiation of BN rats led to a decrease of RT6+ T splenocytes, but by itself (i.e., without exposure to mercury) did not cause autoimmune responses to renal antigens. In addition, gamma-irradiated BN rats treated with mercury had autoimmune responses similar to those observed in mercury-treated nonirradiated controls. Depletion of RT6+ T cells in LEW rats through the use of a monoclonal antibody against the RT6.1 alloantigen did not by itself cause renal autoimmunity in this "resistant" strain. Depletion followed by administration of mercury also failed to induce renal autoimmunity. The lack of autoimmune effects in RT6-depleted BN and LEW rats suggests that a combination of several factors may be necessary to break self-tolerance and cause mercury-induced autoimmunity. Such factors likely comprise both environmental (mercury) and endogenous, genetically determined components. The latter include regulatory T cells (possibly RT6+), major histocompatibility complex (MHC), and T-cell receptors (TCR). Thus, BN rats with decreased percentages of immunoregulatory RT6+ T lymphocytes require additional immunotoxic and/or toxic effects of mercury for autoimmunity to occur. On the other hand, LEW rats depleted of regulatory T cells may still be unable to develop renal autoimmunity after exposure to mercury because they lack the appropriate MHC and TCR.
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PMID:Role of RT6+ T lymphocytes in mercury-induced renal autoimmunity: experimental manipulations of "susceptible" and "resistant" rats. 802 64

Repeated exposure to relatively low doses of mercuric chloride causes a variety of autoimmune responses in rats of the Brown Norway (BN) strain. These animals experience a membranous glomerulonephritis, characterized by the production of autoantibodies to renal antigens (e.g., laminin) and proteinuria. In contrast, Lewis (LEW) rats are "resistant" to the autoimmune effects of mercury. Despite extensive investigations, the mechanisms of immunoregulation in this animal model are still unknown. RT6+ T lymphocytes may have a regulatory role in both BN and LEW rats. This hypothesis is suggested by our finding of a mercury-associated decrease of RT6+ T cells in lymph nodes of BN rats exposed to mercury and the lack of such effect in similarly treated LEW rats. In the present report we show that congenic LEW.1N or BN.1L had no renal autoimmune disease after treatment with HgCl2. FCM analysis of mercury-treated LEW.1N revealed that RT6.1+ T lymphocytes were significantly decreased in both spleen and lymph nodes of these animals. Experimental depletion of RT6+ T cells (by monoclonal antibody treatment or gamma irradiation) in LEW.1N and BN.1L rats did not favor the induction of renal autoimmunity after exposure to mercury. On the other hand, BN-->LEW.1N chimeras (obtained by adoptive transfer of BN lymphocytes into gamma-irradiated LEW.1N rats) experienced autoimmune responses to kidney antigens when treated with HgCl2. They had autoantibodies to laminin and linear binding of immunoglobulins in their kidneys as well as a decreased percentage of RT6.2+ T lymphocytes in cervical lymph nodes. Therefore, the different components of this experimental model can now be dissected using various types of BN-->LEW.1N chimeras, obtained by the adoptive transfer of purified T cell subsets.
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PMID:Mercury-induced renal autoimmunity in BN-->LEW.1N chimeric rats. 816 52

The repeated administration of mercury to rats of the Brown Norway (BN) inbred strain results in a self-limiting production of autoantibodies to renal antigens (e.g., laminin) and autoimmune glomerulonephritis. In contrast, rats of the Lewis (LEW) strain do not develop renal autoimmunity after mercury treatment. Suppressor T-cells and/or the idiotype-anti-idiotype network have been implicated in the control of autoimmunity in susceptible (BN) rats as well as the "resistant" state of nonsusceptible (LEW) animals. In our investigations of the immune regulation of mercury-induced autoimmune glomerulonephritis, we have performed a phenotypic analysis of lymphocyte subpopulation in the spleens and lymph nodes of mercury-treated and control LEW, BN, and (BN x LEW) F1 hybrid rats. Of particular interest were RT6+ T-cells, a subpopulation of lymphocytes that may have immunoregulatory properties and show a relative decrease in mercury-treated BN rats concomitantly with the development of autoimmune responses to renal autoantigens. LEW rats did not develop renal autoimmunity after mercury treatment and had no significant change in the ratio of RT6+ to RT6- T-lymphocytes. Interestingly, the administration of mercury to (BN x LEW) F1 hybrid rats caused effects similar to those observed in the BN strain. Auto-immune responses to antigens of the kidney coincided with a change in the balance within the RT6 cell population, which was altered in favor of T-lymphocytes that do not express the RT6 phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mercury-induced renal autoimmunity: changes in RT6+ T-lymphocytes of susceptible and resistant rats. 835 5

Lethally irradiated Lewis (LEW) rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period, develop, upon withdrawal of CsA, a graft-versus-host-like disease, so-called CsA-induced autoimmunity (CsA-AI). This T cell-mediated autoimmune disease is thymus-dependent; it is generally held that this disease is a consequence of aberrant T cell recovery brought about by CsA. In this study we determined mononuclear cell subsets phenotypically by tri-colour flow cytometry. A strong decrease in recent thymic emigrants (Thy1.1+, TCR alpha beta +) was observed as a consequence of CsA treatment, eventually resulting in decreased absolute peripheral T cell numbers. In these rats no altered CD4:CD8 T cell ratio was observed before onset of CsA-AI; CD4+ and CD8+ cells consisted predominantly of monocytes (CD4dim+, TCR alpha beta-) and natural killer cells (CD8+, TCR alpha beta-), respectively. LEW rats, x-irradiated, syngeneic bone marrow-reconstituted and treated with CsA, showed a marked and persistent, relative expansion of mature CD45RC+, RT6- Th cells. In contrast, Brown-Norway rats treated in a similar fashion, or LEW rats subjected to either CsA treatment or x-irradiation, did not show a comparable expansion of mature CD45RC+, RT6- Th cells, nor did these animals develop CsA-AI. The CD45RC+, RT6- Th cells produced IL-2, and moreover constituted the only Th subset producing IFN-gamma upon stimulation, and therefore were considered as Th1-like effector cells. These results are consistent with the view that a persistent preponderance of Th1 cells and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA-AI will occur.
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PMID:Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-gamma)-producing CD45RC+RT6- T helper cells. 880 39

The results of clinical islet transplantation have remained poor when compared with the consistent success of pancreas transplantation. Autoimmunity has usually been discounted as a cause of islet transplant failure. Previously, we demonstrated that pancreas transplants from the diabetes resistant BB rat (BB-DR) function indefinitely in autoimmune diabetic hosts, but islets from the same donor are vulnerable to recurrent autoimmunity. Addition of 100 million pancreatic lymph node cells (PLNC) to BB-DR islets restores resistance to autoimmunity and leads to repletion of a T cell subset (RT6.1) in the recipients. Autoimmune (BB-Ac) and streptozocin (BB-Sz) diabetic BB rats were recipients of Wistar Furth (WF) intraportal islet or islets plus PLNC transplants with cyclosporine 5 mg/kg/day recipient treatment. One cohort of Brown Norway (BN) islet transplants to BB-Ac with CsA was performed. At the termination of the experiment, recipient peripheral blood lymphocytes (PBL) were characterized by flow cytometry (FACS) for class I, CD4, CD8, RT6.1, and RT6.2, a T cell maturation marker found in WF but not BB rats. All (14/14) WF and 75% (6/8) BN islet transplants to BB-Ac recipients failed after a mean of 42 and 36 days, respectively, despite CsA immunosuppression. WF islets were successful in 6/8 (75%) transplants to BB-Sz recipients (P<0.001 vs. BB-Ac recipients), confirming that autoimmunity is the major cause of islet failure in BB-Ac rats. Addition of PLNC to WF islets increased the survival in BB-Ac to 82% (9/11) (P<0.0001 vs. WF islets alone). Recipients of islet+PLNC express 19.7% RT6.2 compared with 4.6% and 4.0% for WF islets alone in BB-Ac (P<0.01) and BB-Sz (P<0.01), respectively. Autoimmunity is an important factor leading to islet transplant failure in autoimmune diabetic BB rats. Addition of donor PLNC prevent islet allograft failure and leads to recipient chimerism for a donor T cell subset (RT6.2) associated with resistance to autoimmunity.
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PMID:Prevention of autoimmune islet allograft destruction by engraftment of donor T cells. 902 Mar 34

Repeated exposure to mercury causes various autoimmune effects in rats of the Brown Norway (BN) strain. Previous studies from our laboratory have shown that on day 15 of HgCl2 treatment BN rats exhibit a relative decrease in RT6.2+ T cells. At the same time, they produce high levels of autoantibodies to renal antigens and experience a membranous glomerulonephropathy. In contrast, Lewis (LEW) rats are resistant to autoimmunity caused by mercury and do not demonstrate a decrease in RT6+ cells after administration of HgCl2. In the present paper we provide novel information on the correlation between changes in RT6.2+ lymph node T cells and the production of autoantibodies to laminin 1, obtained by detailed kinetic studies of HgCl2-treated BN rats. We have confirmed a decrease in the percentage of RT6.2+ lymphocytes on day 15 of mercury treatment, despite a significant increase in the number of peripheral lymphocytes. No such changes were observed in LEW rats. We have determined that on day 15 the percentage decrease in RT6+ cells is evident in both RT6.2+CD4+ and RT6.2+CD8+ T cell subsets. Kinetic studies demonstrated that significant changes in the percentage of RT6.2+ cells are first observed by day 8 and continue through days 11 and 15. We have also observed a significant percent decrease in CD4+ T lymphocytes as well as an increase in CD4-CD8- cells. The dramatic increase in the percentage of these double negative cells at the level of peripheral lymphoid tissues does not appear to be due to higher thymic output, since there was a decrease in the percentage of TCR+Thy1+ cells, a phenotype that is associated with recent thymic emigrants. Finally, we have demonstrated that 100% of HgCl2-treated BN rats had circulating antibodies that reacted with both mouse and rat laminin 1, i.e. are autoantibodies to laminin 1. These autoantibodies were predominantly of the IgG1 and IgG2a isotype, possibly as the result of a polarized autoimmune response driven by Type 2 cytokines. A kinetic investigation showed that significant levels of IgG1 and IgG2a autoantibodies to laminin 1 were first presentin the circulation by day 11. The inverse correlation between levels of RT6.2+ T lymphocytes and autoantibodies to laminin 1 suggests that mercury may induce autoimmune responses in BN rats by its effects on these immunoregulatory cells.
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PMID:Mercury-induced autoimmunity in Brown Norway rats: kinetics of changes in RT6+ T lymphocytes correlated with IgG isotypes of circulating autoantibodies to laminin 1. 957 Mar 34