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

Injection of a low dose of mercuric chloride into Brown Norway (BN) rats caused a marked decrease in the concanavalin A (ConA)-induced generation of interferon-gamma-producing cells (IFN-gamma pc) in spleen cell cultures prepared 1 h after mercury administration. A second injection 48 h later caused a further diminution of IFN-gamma pc down to 30% of the number generated in splenocyte cultures of phosphate-buffered saline (PBS)-injected controls. Injection of Lewis rats with either one or two doses of HgCl2 revealed no inhibitory effect on splenic IFN-gamma production. The presence of the reduced form of glutathione (GSH) in the culture medium was found to be essential in these experiments. In the absence of GSH there was an overall 20-fold reduction of the number of IFN-gamma pc in splenocyte cultures of normal or PBS-injected rats, which was further reduced to a 60- to 70-fold-lower level in cultures of rats exposed to HgCl2. This mercury-mediated extra reduction could be fully reversed with an excess (2 mM) of GSH in Lewis but not in BN splenocyte cultures. Since the bivalent Hg2+ ion is known to bind to and inactivate sulfhydryl groups of proteins and low molecular weight thiols, most notably GSH, we investigated a possible role for thiols in IFN-gamma production. It was found that the generation of IFN-gamma pc in normal BN and Lewis splenocyte cultures was strongly dependent on GSH or its precursor cysteine in the culture medium. Other thiol compounds were also effective but disulfides were completely inactive. Depletion of intracellular GSH in ConA-stimulated splenocytes by buthionine sulfoximide (BSO), an inhibitor of de novo GSH biosynthesis, strongly inhibited the generation of IFN-gamma pc. The inhibitory effect of BSO was not abolished by the addition of interleukin-2 (IL-2), but was mimicked with antibodies directed to the IL-2 receptor. The data stress the importance of GSH in the enhancement of IL-2-mediated IFN-gamma production and are most consistent with a model in which mercury interferes with T cell IFN-gamma production by affecting the intracellular availability of GSH. The strain-specific susceptibility to mercury-mediated inhibition of IFN-gamma production is discussed.
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PMID:Mercuric chloride down-regulates T cell interferon-gamma production in brown Norway but not in Lewis rats; role of glutathione. 844 15

Human recombinant interleukin-10 (IL-10) was previously shown to inhibit accessory cell (AC)-dependent proliferation of bovine parasite-specific T helper 1 (Th1), Th2, and Th0 cells in an IL-2-reversible manner (Brown, W.C., Woods, V.M., Chitko-McKown, C.G., Hash, S.M., and Rice-Ficht, A.C., 1994. Infect. Immun. 62, 4697-4708). The present study was therefore designed to determine whether the effect of IL-10 on T cell proliferation corresponded with downregulated expression of cytokines, or their receptors, important for T cell growth. The effects of IL-10 on cellular proliferation and expression of IL-2, IL-4, IL-2 receptor (IL-2R; p55), and IFN-gamma by Babesia bovis- or Fasciola hepatica-specific Th cell clones were simultaneously evaluated. As shown previously, IL-10 strongly inhibited proliferation of all types of Th cell clones, although this did not correspond with reduced expression of IL-2 or IL-4 mRNA or their products. In contrast, expression of IL-2R mRNA was consistently reduced in the IL-10-treated clones. These results indicate that IL-10 does not inhibit AC-dependent proliferation of bovine Th cells by downregulating T cell cytokines; rather, IL-10 may act by downregulating IL-2R p55 expression and subsequent signal transduction leading to decreased cellular proliferation. IFN-gamma production was also consistently downregulated in the presence of IL-10.
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PMID:Interleukin-10 downregulates proliferation and expression of interleukin-2 receptor p55 chain and interferon-gamma, but not interleukin-2 or interleukin-4, by parasite-specific helper T cell clones obtained from cattle chronically infected with Babesia bovis or Fasciola hepatica. 856 14

Worm expulsion of, and IgE and interferon (IFN)-gamma responses to, Nippostrongylus brasiliensis were studied in 2 rat strains, Brown Norway (BN) and Fischer (F)-344. BN rats expelled the majority of worms by day 14 post-infection (p.i.) with approximately 6% of worms surviving for at least 3 weeks. In F-344 rats, worm expulsion was delayed by 2 days relative to that in BN, while the numbers of residual worms were significantly fewer than in BN, suggesting that different immune mechanisms are involved in early and late phases of immunity. Total serum IgE, as well as in vitro IgE production by mesenteric lymph node (MLN) cells, was increased 2 weeks p.i., the levels being markedly higher in BN than in F-344 rats. Serum rat mast cell protease II was also increased more significantly in BN than in F-344 rats. In contrast, production of IgG2a and IFN-gamma by MLN and spleen cells was found to be higher in F-344 than in BN rats. These results indicate that the early worm expulsion is correlated with the host IgE and mast cell responsiveness, whereas the persistence of infection in the late period may be controlled by different immune mechanisms.
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PMID:Dissociation of early and late protective immunity to the nematode Nippostrongylus brasiliensis in Brown Norway and Fischer-344 rats. 872 98

It is now currently thought that Th1 autoreactive cells may induce organ specific autoimmune disease and in these situations Th2 cells are considered as regulatory cells. However, in other situations Th2 cells may be pathogenic. Thus, some chemicals (HgCl2, gold salts or D-penicillamine) may induce Th2-mediated systemic autoimmune disorders in susceptible Brown-Norway (BN) rats. In contrast, HgCl2 induces non antigen specific immunosuppression in Lewis (LEW) rats and protects this strain against organ-specific autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE). Anti-self MHC class II T cells have been detected in both susceptible and resistant strains upon exposure with these chemicals. Autoreactive T cell lines that recognize self MHC class II molecules have been derived from gold salt-injected BN rats (BNAu lines) and from HgCl2-injected LEW rats (LEWHg lines). BNAu T cell lines produced IL-4 and transferred antibody-mediated autoimmunity in BN rats deprived of CD8+ cells. In contrast, HgCl2 protects susceptible rats from Th1-mediated autoimmunity, (autoimmune uveoretinitis). LEWHg lines produced IL-2, IFN-gamma and TGF-beta and were able to protect LEW rats against cell-mediated autoimmunity (EAE) and (LEW x BN)F1 hybrids from antibody-mediated, HgCl2-induced autoimmunity. Several points will be discussed: the specificity of these autoreactive T cells, the mechanisms by which chemicals may induce these cells and the mechanisms by which the immune system maintains or reestablishes self tolerance in rats exposed to these agents.
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PMID:Th2 and Th1 autoreactive anti-class II cell lines in the rat suppress or induce autoimmunity. 873 66

Mast cells have been reported to secrete a wide range of immunoregulatory cytokines following IgE-mediated activation and to play an important role in allergic inflammation. We have previously demonstrated that mast cells can also produce certain cytokines following activation with bacterial LPS or prostanoids without preformed mediator release. IL-12 is a potent inducer of IFN-gamma production by T cells and NK cells, and is thought to play a critical role in determining the nature of the local immune response to infection. We here report that highly purified peritoneal mast cells from Brown Norway rats will produce IFN-gamma in response to IL-12 without significant histamine release. IFN-gamma protein was detected by ELISA in supernatants of mast cells cultured with 2 U/ml recombinant mouse IL-12 for between 6 and 24 h. The production of IFN-gamma was dependent on the dose of IL-12 and was significantly inhibited by concurrent treatment with IL-10 or PGE2. Supernatants from IL-12-stimulated mast cells induced MHC class II expression on the mouse epithelial cell line, MODE-K, by an IFN-gamma-dependent mechanism. Peritoneal mast cells cultured following activation with anti-IgE or LPS, under conditions that will induce the production of IL-6, demonstrated no detectable protein production of IFN-gamma. We conclude that mast cells are capable of contributing to the IFN-gamma response to IL-12, but substantial mast cell IFN-gamma production does not occur as a result of IgE-mediated activation. These observations have important implications for the role of the mast cell in local immune regulation.
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PMID:Rat peritoneal mast cells produce IFN-gamma following IL-12 treatment but not in response to IgE-mediated activation. 875 36

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

To assess whether Th-2 cytokines are involved in the late airway response (LR) after antigen challenge, we evaluated cytokine mRNA expression in the lungs of two strains of rats before and 8 h after saline or antigen challenge: Brown Norway (BN) rats, high IgE producers that develop LR after antigen challenge and Sprague-Dawley (SD) rats, low IgE producers that develop little LR and no increased airway responsiveness after antigen challenge. Rats were sensitized with ovalbumin (OA) and 14 days later, lungs were obtained before or after OA challenge and measurement of lung physiology for 8 h. Lung tissue was either fixed for in situ hybridization or frozen for evaluation of mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). We examined mRNA expression for interleukin-4 (IL-4), and IL-5 (Th-2 cytokines) and IL-2 and interferon gamma (IFN-gamma, Th-1 cytokines). In situ hybridization showed that cells expressing IL-4 and -5 mRNA were increased in the airways of the lungs of BN rats after OA challenge (P < 0.05) and that cells expressing mRNA for IFN-gamma and IL-2 were higher in SD than in BN rats after antigen challenge (P < 0.05). Results from PCR showed that prior to antigen challenge, BN rats expressed in their lungs mRNA for IL-4 and -5 and SD rats expressed very little mRNA for IL-5 only. After antigen challenge most BN and SD rats expressed mRNA for IL-4 and -5 but expression of mRNA for IL-2 and IFN-gamma was only found in SD rats. In conclusion, rats that develop a LR after antigen challenge preferentially increase Th-2 cytokine expression in their lungs whereas those without LRs preferentially express Th-1 cytokines. Our results support the role of Th-2 cytokines in the LR and asthma.
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PMID:Cytokine expression in the presence or absence of late airway responses after antigen challenge of sensitized rats. 881 Jun 41

Previous work has shown that in vitro exposure of Brown-Norway (BN) rat peritoneal mast cells to mercuric chloride (HgCl2) causes enhancement of subsequent mediator release induced by cross-linking of surface immunoglobulin E (IgE). This enhancing effect is seen significantly less often with peritoneal cells from Lewis rats. In addition HgCl2 has been shown to suppress interferon (IFN)-gamma production by BN but not Lewis splenocytes. Given that IFN-gamma is known to inhibit mediator release by mast cells, we hypothesized that the strain difference in the effect of HgCl2 on mediator release was mediated via a differential effect on IFN-gamma release from T cells in the mixed peritoneal cell population: IFN-gamma release would be suppressed in the case of the BN rat, releasing the mast cells from inhibition and resulting in the enhancing effect of HgCl2. The aim of the study was to test two predictions of this hypothesis. Exposure of BN rat mast cells to IFN-gamma inhibited subsequent antigen-induced mediator release but did not significantly reduce HgCl2-mediated enhancement of this release. Exposure of Lewis rat mast cells to blocking concentrations of anti-IFN-gamma did not reveal any HgCl2-mediated enhancement of mediator release. These observations provide strong evidence against the hypothesis that the differential effects of HgCl2 on BN and Lewis rat mast cells are mediated via IFN-gamma. In addition the results revealed that BN rat mast cells are significantly more sensitive than Lewis rat mast cells to the inhibitory effects of IFN-gamma on antigen-induced mediator release.
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PMID:The strain difference in the effect of mercuric chloride on antigen-triggered serotonin release from rat mast cells is not mediated via interferon-gamma. 895 63

In Brown Norway to Lewis rat lung transplantation, short-term administration of cyclosporine produces permanent adoption of allografts; however, the adopted grafts show symptoms of chronic rejection. To clarify the difference in cytokine production in acute an chronic rejection of the allografts, an immunohistochemical study was performed. In acute rejection, positive cells for respective cytokines were observed in infiltrating cells, increasing in number as the days after transplantation passed, and reaching a maximum on the fifth day. The strongest reactivity was observed perivenously. In chronic rejection, TNF-alpha positive cells were observed in the perivascular and peribronchial regions, especially around class II positive epithelia. The number of positive cells was, however, less than that in the vascular phase of acute rejection. Few cells were positive for IL-1 beta, IFN-gamma and, unexpectedly, for IL-4. These facts indicate the functional difference of infiltrating cells between acute and chronic rejection.
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PMID:Difference in cytokine production in acute and chronic rejection of rat lung allografts. 895 33

Autoreactive anti-MHC class II T cells are found in Brown Norway (BN) and Lewis (LEW) rats that receive either HgCl2 or gold salts. These T cells have a T helper cell 2 (Th2) phenotype in the former strain and are responsible for Th2-mediated autoimmunity. In contrast, T cells that expand in LEW rats produce IL-2 and prevent experimental autoimmune encephalomyelitis, a cell-mediated autoimmune disease. The aim of this work was to investigate, using T cell lines derived from HgCl2-injected LEW rats (LEWHg), the effect of these autoreactive T cells on the development of Th2-mediated autoimmunity. The five LEWHg T cell lines obtained protect against Th2-mediated autoimmunity induced by HgCl2 in (LEW x BN)F1 hybrids. The lines produce, in addition to IL-2, IFN-gamma and TGF-beta, and the protective effect is TGF-beta dependent since protection is abrogated by anti-TGF-beta treatment. These results identify regulatory, TGF-beta-producing, autoreactive T cells that are distinct from classical Th1 or Th2 and inhibit both Th1- and Th2-mediated autoimmune diseases.
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PMID:Transforming growth factor beta (TGF-beta)-dependent inhibition of T helper cell 2 (Th2)-induced autoimmunity by self-major histocompatibility complex (MHC) class II-specific, regulatory CD4(+) T cell lines. 915 2


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