Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mercuric chloride (HgCl2) induces in Lewis (LEW) rats a non-antigen-specific immunosuppression and is able to down-modulate experimental allergic encephalomyelitis in about 70% of the rats. The aim of the present study was to determine the frequencies of lymph node cells involved in the proliferative response to myelin basic protein in rats injected with HgCl2 and immunized with myelin by using limiting dilution analysis (LDA). Highly frequent CD8+ T suppressor cells and at least 10-fold less frequent protein basic-specific T helper cells were detected in these rats. A third cell type allowing the proliferative response of Th cells in spite of Ts cells was also demonstrated. These cells, which could act as contrasuppressor cells, were CD4+ and adhered to Vicia villosa lectin; their frequency was in the same range as that of T helper cells. These data illustrate the potential role of different levels of T cell immunoregulatory activity in autoimmunity and the major interest of LDA in their analysis.
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PMID:HgCl2-induced perturbation of the T cell network in experimental allergic encephalomyelitis. I. In vitro characterization of T cells involved. 171 19

In the companion paper (J. Rossert et al., Cell. Immunol. 137, 1991), we showed by using limiting dilution analysis that Lewis (LEW) rats injected with HgCl2 and immunized with myelin (LEWHg/MYE) exhibit anti-basic protein CD4+ T helper cells (Th), at least 10-fold more frequent CD8+ T suppressor cells (Ts), and T contrasuppressor cells (Tcs). These Tcs cells were shown to be CD4+ T cells adhering to Vicia villosa (VV) lectin and allowed Th cells to proliferate despite the presence of Ts cells. The CD8+ Ts cells might be responsible for the protection from experimental allergic encephalomyelitis (EAE) observed in about 70% of LEW rats injected with HgCl2. The concomitant presence of CD4+ Tcs cells might explain that 30% of the rats escaped this protection. The aim of this work is to demonstrate in vivo the roles of CD8+ Ts cells and Tcs cells in mercury-induced protection from EAE. It will be shown that LEWHg/MYE rats depleted of CD8+ cells as well as LEWHg/MYE rats transferred with VV lectin-adherent Tcs cells develop EAE. These data demonstrate that CD8+ Ts cells are responsible for HgCl2-induced protection and that Tcs cells are involved in the control of Ts cells in vivo.
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PMID:HgCl2-induced perturbation of the T cell network in experimental allergic encephalomyelitis. II. In vivo demonstration of the role of T suppressor and contrasuppressor cells. 183 85

HgCl2 induces autoimmunity in Brown-Norway rats and immunosuppression in Lewis rats. In the latter rats, HgCl2 triggers the proliferation of T suppressor/cytotoxic (OX8+) cells which actively suppress T cell functions. This led us to study the effect of HgCl2 on experimental allergic encephalomyelitis (EAE), a T cell-mediated autoimmune disease obtained following immunization with basic protein (BP). It will be shown that HgCl2 attenuates or even prevents clinical manifestations of EAE and inhibits both the proliferative response of T cells to BP and the anti-BP antibody response. This immunosuppression was not due to a defect at the T helper cell or antigen-processing cell level but to the emergence of T suppressor cells.
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PMID:Effect of HgCl2 on experimental allergic encephalomyelitis in Lewis rats. HgCl2-induced down-modulation of the disease. 245 Jul 57

Brown-Norway (BN) rats are uniquely susceptible to development of autoimmune phenomena and enlargement of lymph nodes and spleen after repeated injections of mercuric chloride. Despite its ability to produce autoimmunity, HgCl2 inhibited the development in BN rats of experimental allergic encephalomyelitis (EAE), another autoimmune process. The inhibition by mercury was probably due to lack of the normal absorption and granulomatous reaction to the EAE inoculum in the enlarged lymph nodes draining the inoculation site. Lewis rats did not develop enlarged nodes from HgCl2 treatment. Lewis lymph nodes absorbed the EAE inoculum abundantly and developed an extensive granulomatous reaction despite the mercury treatment, and there was only a slight inhibition of EAE. Therefore, the ability of HgCl2 to produce lymphadenopathy in BN rats may be responsible for the inability of these rats to absorb the inoculated antigen. The mercury-induced failure of absorption was manifested as an inhibition of EAE in BN rats.
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PMID:Suppression of experimental allergic encephalomyelitis in rats by mercuric chloride. 278 62

The phosphodiesterase inhibitor oxpentifylline (OXP) has a number of potentially important immunomodulatory actions which include a selective inhibition of the Th1 subset of CD4+ cells in vitro and inhibition of tumor necrosis factor (TNF)-alpha mRNA transcription. In vivo, it has a dramatic protective effect against experimental allergic encephalomyelitis. In this animal model, tissue injury is associated with both a Th1 response and with TNF-alpha production, either of which could be targets for the protective action of OXP. In an attempt to clarify the relative importance of the Th cell subsets and TNF-alpha in pathogenesis, we investigated the effect of OXP on a Th2 model of T cell-dependent disease, mercuric chloride (HgCl2)-induced autoimmunity in the Brown Norway rat. The effects of OXP on the Th1:Th2 response, TNF-alpha mRNA transcription in spleen and ankle joints, and on the incidence and severity of arthritis and cecal vasculitis have been examined and the effects in vivo have been compared with those of a soluble TNF receptor-IgG1 fusion protein (sTNFR) that neutralizes rat TNF-alpha. In two separate experiments, OXP significantly enhanced unstimulated levels of splenic interleukin-4 (IL-4) mRNA (median 62%, of an artificial IL-4 mRNA construct, vs. 36.5% in controls) and in one experiment, exaggerated the total IgE response to HgCl2. OXP inhibited HgCl2-induced TNF-alpha mRNA transcription in spleen and ankle joints. In three separate experiments, OXP had a significant protective effect against arthritis, with the mean incidence reduced from 100% to 30% and mean peak score reduced from 7.2 to 2.59 (experiments 1 and 2). The protection against arthritis was indistinguishable from that produced by sTNFR. There was no such protection against cecal vasculitis with either OXP or sTNFR. These results demonstrate that OXP induces a shift towards a Th2 response, inhibits TNF-alpha mRNA transcription locally in joint and systemically in spleen, and has a protective effect against arthritis similar to that produced by sTNFR in the HgCl2-treated BN rat. We conclude that TNF-alpha is a critical cytokine in the pathogenesis of arthritis but not cecal vasculitis in this model, and that inhibition of TNF-alpha transcription is the most important mode of action of OXP in this situation. OXP may be a potential therapeutic agent in the treatment of other arthritides, such as human rheumatoid arthritis, in which TNF-alpha has been implicated in pathogenesis.
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PMID:Oxpentifylline inhibits tumor necrosis factor-alpha mRNA transcription and protects against arthritis in mercuric chloride-treated brown Norway rats. 758 90

Brown-Norway (BN) rats injected with HgCl2 develop a systemic autoimmune disease associated with a polyclonal B cell activation, due to autoreactive T cells specific for self-class II molecules, while Lewis (LEW) rats injected with HgCl2 do not exhibit autoimmunity and develop a non-antigen-specific, CD8-mediated immunosuppression assessed by a depression of T cell functions, and a protection against experimental autoimmune encephalomyelitis (EAE). Resistance to HgCl2-induced autoimmunity is not due to these suppressor cells since treatment with an anti-CD8 monoclonal antibody (mAb) did not allow autoimmunity to appear. The absence of autoimmunity in this strain could result from the absence of autoreactive T cells, or from quantitative or qualitative differences of these cells between susceptible and resistant strains. In the present study, we show that CD4+ anti-class II T cells are present in HgCl2-injected LEW rats and are as frequent as in BN rats when assessed by limiting dilution analysis. LEW CD4+ autoreactive T cell lines were derived. They proliferated in the presence of normal class II-bearing cells, secreted interleukin 2, and did not induce B cells to produce immunoglobulins. Transfer of one of these lines, LEW Hg A, into normal LEW rats led to the appearance of CD8+ cells responsible for a non-antigen-specific immunosuppression that induced complete protection from EAE. Immunosuppression was abrogated after treatment with an anti-CD8 mAb. In vitro, CD8+ cells from rats injected with the LEW Hg A T cell line proliferated in the presence of activated T cells whatever their origin. We conclude that HgCl2 induces CD4+ autoreactive T cells that proliferate in the presence of class II+ cells in susceptible BN as well as in resistant LEW rats. But while these cells collaborate with B cells to produce autoantibodies in BN rats, they initiate in LEW rats a suppressor circuit involving antiergotypic CD8+ suppressor cells.
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PMID:Mercury-induced autoreactive anti-class II T cell line protects from experimental autoimmune encephalomyelitis by the bias of CD8+ antiergotypic cells in Lewis rats. 809 39

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

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

Repeated exposure of Brown Norway (BN) rats to relatively low doses of HgCl2 induces autoantibodies to renal antigens (e.g., laminin) and a membranous glomerulonephropathy characterized by proteinuria. In contrast, Lewis (LEW) rats are "resistant" to the autoimmune effects of mercury and, when exposed to this metal, are protected against experimental autoimmune encephalomyelitis (EAE) and Heymann's nephritis. To date, there is no information on "suppressive" effects of mercury in naturally occurring (so-called "spontaneous") rat models of autoimmune disease. Therefore, we have administered HgCl2 to diabetes-prone (DP) BB rats, animals that spontaneously develop both insulin-dependent diabetes mellitus (IDDM) and thyroiditis. We found that DP rats treated with mercury or water for a period of 40-125 days developed autoantibodies to thyroglobulin, with a higher incidence in HgCl2-injected animals (92% vs. 56% in H2O-injected controls). A novel finding of our study was the detection of autoantibodies to laminin in the same rats, again with an increased incidence after HgCl2 treatment (83% vs. 44%). IgG2a was the most frequently detected isotype of antibodies to laminin, followed by IgG1, IgG2b and IgG2c. The IgG isotype profile suggests that treatment with HgCl2 may activate both Th1 and Th2 lymphocytes in BB rats. In spite of these stimulatory effects on autoantibody responses, we found that there was no difference in the incidence of IDDM and thyroiditis between HgCl2-treated and control animals. We conclude that the suppressive effects of mercury previously observed in EAE and Heymann's nephritis of LEW rats do not occur in "spontaneous" autoimmune IDDM and thyroiditis of BB rats. Therefore, immune suppression caused by HgCl2 cannot be considered a common phenomenon, but may be a genetically determined characteristic of LEW rats, possibly related to a specific or unique cytokine profile of this particular rat strain. In contrast, while mercury does not seem to recruit, induce or rescue regulatory T cell function in DP rats, it does stimulate autoantibody responses in these animals.
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PMID:Effects of HgCl2 on the expression of autoimmune responses and disease in diabetes-prone (DP) BB rats. 955 Feb 85

Injection of Brown-Norway rats with mercuric chloride (HgCl2) activates a T helper type 2 (Th2) autoimmune response, with production of a number of autoantibodies and vasculitis primarily affecting the gut. Glucocorticoids have been shown to suppress Th1 and to promote the development of Th2-type responses. Conversely dehydroepiandrosterone (DHEA) promotes Th1 responses with suppression of Th2 responses. This study set out to define the role of these hormones in this animal model. Rats were adrenalectomized (Adx) with no steroid replacement (n = 11), Adx with basal steroid replacement given by a 25 mg corticosterone pellet inserted subcutaneously (n = 13), or sham-Adx (n = 14) prior to administration of HgCl2. In both groups of Adx animals there was a delay in the production of immunoglobulin E (IgE) and serum concentrations on day 9 were marginally lower (P = 0.035, repeated measures ANOVA). All of the animals Adx with no steroid replacement and two Adx animals with steroid replacement died between 10 and 14 days after HgCl2 challenge. There was no difference in the severity of caecal vasculitis between the groups. A significant increase in adrenal size was noted following administration of HgCl2. Administration of subcutaneous DHEA implants (100 mg and 200 mg) had no significant effect on IgE concentrations or severity of vasculitis. These observations do not support the hypothesis that corticosterone and DHEA play a central role in setting the Th1/Th2 balance in this experimental Th2-mediated autoimmune disease; in contrast with the Th1-mediated autoimmune disease experimental allergic encephalomyelitis where corticosterone plays a key role in immunoregulation.
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PMID:The role of endogenous steroid hormones in the generation of T helper 2-mediated autoimmunity in mercuric chloride-treated Brown-Norway rats. 1065 52


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