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)

Immunization with antigen-specific T cells has been used successfully in the treatment of several T cell-mediated experimental autoimmune diseases, including experimental allergic encephalomyelitis, thyroiditis, and adjuvant arthritis. The aim of this study was to determine whether T-cell vaccination could be used to down-regulate specifically the antibody response to AChR in experimental autoimmune myasthenia gravis (EAMG), an antibody-mediated disorder. We produced T cells specific for the acetylcholine receptor (AChR) by immunizing Lewis rats with torpedo AChR, harvesting the regional lymph node cells, and restimulating them in vitro with AChR. This cell population was expanded with IL2. The cells were then activated with concanavalin A (Con-A) and exposed to high hydrostatic pressure to augment their immunogenicity. We found that rats vaccinated with these cells did not manifest decreased antibody titers to AChR, when challenged. In fact, the antibody response to AChR was consistently potentiated by the vaccine treatment. This result could not be attributed to antigen carryover by the vaccinating cells or to induction of anti-idiotypic antibodies. Despite these results showing overall enhancement of the AChR antibody response, we found evidence of AChR-specific suppressor cells in the spleens of the vaccinated animals. Our observations indicate that T-cell vaccination can elicit both a positive immune response and a suppressive response in the same animal. If the T-cell vaccination strategy is to be useful for the treatment of MG, methods for amplifying the suppressive effect will need to be developed.
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PMID:T-cell vaccination in experimental myasthenia gravis: a double-edged sword. 215 Sep 10

Recognition of self protein epitopes, apart from those engaged in idiotypic network interactions and MHC restriction, is probably a physiological event in the normal functioning immune system. Furthermore T and B cells recognizing self antigens can be easily cloned from healthy individuals and sometimes be shown to confer autoimmune disease by passive transfer in the experimental situation. The issue is how potentially autoaggressive cells can become activated and how such activity can be contained safely. Experimentally, autoimmune disease can be evoked by immunization with autoantigens (encephalomyelitis, thyroiditis etc.) or with foreign antigens that feature antigenic relationships with self antigens (adjuvant arthritis). In both situations transfer of disease has been shown with cloned T cells of a single specificity. In addition, specific control of disease using the same cloned T cells has been achieved. Adjuvant arthritis has been illustrative in these respects. By means of specificity analysis of cloned T cells, a 65 kD heat shock protein of mycobacteria was identified as crucial in the disease. Immunization with this antigen has been found to prevent the development of disease, including forms elicited without mycobacterial involvement. Furthermore, vigorous immunological responses to HSP65 were found both in experimental animals and also in humans as a consequence of exposition to various infectious organisms. By their conserved nature HSPs have ample potential for dangerous mimicry. Recent evidence accumulated suggesting that the same HPS65 may be crucial in human chronic arthritis as well. Therefore it is hoped that extrapolation of the experimental findings to the human situation will help the development of specific means, either T cells or antigens, to control spontaneous autoimmune arthritis in man.
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PMID:Heat-shock proteins in autoimmune arthritis: a critical contribution based on the adjuvant arthritis model. 219 35

Viruses can initiate disease by many different means. Direct viral, immune mediated and host factors all play important parts. Molecular mimicry or having cross-reacting determinants that result in immune responses which have the potential to cause damage can be incorporated into this framework. Here, autoimmune responses generated by virus infection have been presented in relation to these other parameters. The cross-reacting immune response originally generated by virus would have to be directed toward or involve a disease inducing site such as an EAE (encephalitogenic), thyroiditis, or diabetogenic site. If the cross-reaction took place at a nondisease inducing site, the ensuring immune response may result in the production of autoantibodies, however no disease would occur. In other systems autoantibodies can potentiate an ongoing inflammatory response. This may be the case that is described here with Theiler's murine encephalomyelitis virus infection. Lastly, viruses having common determinants with MHC determinants may modify immune responses leading to immunosuppression and allowing virus to persist. In addition, similar determinants may lead to disease by an alternative route. For example, we have described a region of human cytomegalovirus that has a common determinant with HLA DR beta chain. This region is associated with diabetes in humans (Todd et al. 1988). Thus, many factors are involved in the outcome of disease induction by viruses of which autoimmunity is one.
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PMID:Is Theiler's murine encephalomyelitis virus infection of mice an autoimmune disease? 253 48

The induction of autoimmune diseases in animals was studied with Legionella and mycobacteria as adjuvants, emulsified in oil with antigen extracts of thyroid, testis, spinal cord, and peripheral nerve. Both adjuvants were equally effective in inducing delayed hypersensitivity and humoral antibody to the tissue antigens. The Legionella adjuvant, however, induced little or no thyroiditis and aspermatogenesis, whereas the mycobacterial adjuvant induced thyroiditis and aspermatogenesis. Both adjuvants caused allergic encephalomyelitis and peripheral neuritis. The results indicated that delayed hypersensitivity by itself may not be sufficient to cause thyroiditis and aspermatogenesis. Legionella adjuvant apparently lacked the ability to induce certain immune factor(s) which caused the disease in experimental thyroiditis and aspermatogenesis. The differential properties of Legionella adjuvant and mycobacterial adjuvant in inducing immunity to autoantigens could provide a useful means to study the pathogenic and immunoregulatory mechanisms of some experimental autoimmune diseases.
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PMID:Induction of autoimmune diseases with adjuvants: separation of delayed hypersensitivity and antibody formation from diseases in experimental thyroiditis and aspermatogenesis with Legionella adjuvant. 300 68

The material presented here summarizes the bulk of the presently available immunologic data bearing upon the in vivo relationship between brown adipose tissue and the immune system. The experiments were carried out in rats adipectomized (by surgical excision of the interscapular brown adipose tissue at birth), thymectomized (by neonatal removal of the thymus), adipectomized and thymectomized, and corresponding sham-operated controls. The following immune phenomena were studied: antibody production to soluble and corpuscular antigens; Arthus and delayed hypersensitivity skin reactions to bovine serum albumin; rejection of allogeneic skin and thyroid grafts; lymph node enlargement in a host-versus-graft reaction; experimental allergic encephalomyelitis and thyroiditis; immune response in normal animals treated with extracts from brown adipose tissue; allergic encephalomyelitis in thymoadipectomized animals; plaque-forming cell response and hemagglutinating antibody titers in animals injected with met-enkephalin and leu-enkephalin; and survival rate of adipectomized mice inoculated with Sarcoma-I cells. The results indicated that the cell-mediated immune reactions were potentiated in adipectomized rats. Antibody production was not significantly changed by neonatal adipectomy. Adipectomized mice, inoculated with Sa-I tumor cells, survived longer than controls, thus indicating that adipectomy made possible the recognition of discrete histocompatible differences between Sa-I cells and A/JAX mice. Adipectomy increased the ability of rats to develop autoimmune diseases. Saline extracts from brown adipose tissue of newborn rats suppressed hypersensitivity skin reactions in normal adult rats. Thymoadipectomized rats showed an almost normal ability to develop allergic encephalomyelitis, a finding that suggested that the potentiating influence of adipectomy on encephalomyelitis was neutralized by thymectomy. It appears that brown adipose tissue functions as a natural antagonist of the thymus. Enkephalins were found to be more effective immunosuppressors in adipectomized than in normal animals. The last finding establishes a functional link between brown adipose tissue and neuropeptides. It seems that the potentiation of immune response in adipectomized animals is effected by altered release of yet unidentified mediators and modulators. The evidence indicates that brown adipose tissue, in which neurohumoral activity occurs, may be an important component of an integrated immunoneuroendocrine system.
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PMID:Brown adipose tissue. Its in vivo immunology and involvement in neuroimmunomodulation. 330 Apr 71

Cyclosporine is an 11 aminoacid cyclic peptide of fungal origin endowed with potent immunosuppressive activity. Unlike the conventional immunosuppressants, cyclosporine does not interfere with DNA metabolism, but it selectively and reversibly inhibits lymphocyte T-helper activation by inhibiting the production of interleukin-2 which plays a role in immune response development. Cyclosporine has little effect on lymphocytes B and does not modify the production of antibodies when it is in progress. The drug is effective in preventing spontaneous or autoantigen-induced auto-immune diseases in animals. The best studied models are experimental allergic encephalomyelitis, uveitis in the rat and spontaneous diabetes of BB rats. However, cyclosporine has no effect on diseases exclusively due to the pathogenic action of antibodies, such as spontaneous thyroiditis of the obese chicken. It is also possible to obtain a curative effect, this type of model being nearer to therapeutic conditions in humans than the previous models.
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PMID:[Cyclosporin and autoimmune diseases. 1: Experimental bases]. 355 Sep 87

Availability of a line of rabbits deficient in the sixth complement component (C6-D) made it possible to evaluate the role of the terminal complement complex (TCC) in the development of experimental autoimmune thyroiditis (EAT) of the rabbit. Immunization with saline extract of homologous thyroid, known to be composed predominantly of thyroglobulin, led in normocomplementemic (NC) rabbits to severe thyroiditis, with cellular infiltrates occupying 50-95% of the thyroid, and to minimal or moderate thyroiditis, with 1-35% of thyroids infiltrated in C6-D rabbits. Cellular infiltrates consisted predominantly of mononuclear cells with appreciable numbers of granulocytes. Destruction of thyroid follicles was extensive and diffuse in NC rabbits, but it was only minimal and focal in C6-D rabbits. Immunohistology revealed in both groups of rabbits deposits of IgG and C3 along follicular basal laminae. In addition, NC rabbits showed deposition of C6 and MAC in thyroid follicles. These results suggested that TCC is necessary for the development of fully expressed, severe EAT; simultaneously, however, they showed that a significantly reduced EAT can develop without TCC. Administration of NC but not of C6-D rabbit serum to C6-D rabbits resulted in a significant increase in the severity of EAT. It was also shown that C6-D rabbits have "normal" T-cell activity, since they developed experimental autoallergic encephalomyelitis as readily as NC rabbits. Therefore, it is likely that development of EAT is indeed impaired by the C6 deficiency in rabbits. The requirement for TCC observed in this study may be relevant to the understanding of the pathogenesis of Hashimoto's thyroiditis, in which thyroid tissue was recently shown to contain TCC deposits.
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PMID:Role of late complement components in experimental autoimmune thyroiditis. 844 70

Multiple sclerosis (MS) is a chronic demyelinating disease of the human central nervous system (CNS) which can be characterized clinically by a remitting-relapsing or a chronic progressive course. There is a striking similarity between the clinical and histopathological features of MS and the experimentally induced disease, experimental autoimmune encephalomyelitis (EAE). Induced by the injection of myelin basic protein (MBP) and adjuvants, EAE is characterized by clinical neurologic signs of paralysis and histopathologic changes consisting of perivascular mononuclear infiltration and demyelination. We have reported that the oral administration of MBP exerts a profoundly suppressive effect on EAE induced in the Lewis rat. This MBP-induced oral tolerance is characterized by an inhibition of EAE clinical neurologic signs, reduced CNS histopathologic changes, a profound decrease in the T-lymphocyte proliferative response specific for the fed antigen, and a decrease in serum antibody specific for MBP. In a chronic relapsing model of EAE in the B10.PL mouse, we have shown that the oral administration of MBP either prior to MBP challenge or on the first day of clinical signs results in a decreased number and severity of EAE relapses. The oral tolerance approach has also proven effective in the suppression of other organ-specific autoimmune diseases including collagen-induced arthritis, adjuvant arthritis, uveoretinitis, experimental myasthenia gravis, diabetes, and thyroiditis as well as graft rejection. Two primary mechanisms have been proposed to explain oral tolerance in EAE-active suppression following feeding of lower doses of antigen and clonal anergy or deletion following administration of higher doses. In vivo approaches in rats and transgenic mice have been used to further explore the mechanisms underlying oral tolerance. Administration of recombinant interleukin (IL)-2 was shown to reverse the tolerance induced by feeding low doses of MBP, but not the tolerance induced by feeding high doses of MBP, indicating that deletion had occurred in the high-dose group. Moreover, the oral administration of MBP to MBP-specific T-cell receptor (TCR) transgenic mice resulted in a profound decrease of the transgenic T cells in the blood, lymph node cells (LNC), mesenteric LNC, and spleen compartments. The proliferative response to MBP was also profoundly reduced in these organs, indicating that the cells had been deleted from these sites. The results achieved in animal models have led to clinical trials of oral tolerization in three human autoimmune diseases--MS, uveoretinitis, and rheumatoid arthritis--with promising results.
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PMID:Treatment of autoimmune disease by oral tolerance to autoantigens. 881 Oct 61

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

Since Morton and Siegel's epochal experiments 30 years ago animal models have been successfully utilized both for transfer and resolution of autoimmune diseases (AID). More recently human lymphocyte xenografts have reproduced clinical AID in SCID mice. Allogeneic stem cell transplantation demonstrated therapeutic potential in fully developed autoimmune disease. Mixed allogeneic chimerism induced by a sublethal approach has also been shown to prevent and even reverse autoimmune insulitis in nonobese diabetic (NOD) mice. More unexpectedly it was found that experimental adjuvant arthritis (AA) and experimental allergic encephalomyelitis (EAE) could be cured by means of total body irradiation (TBI) followed by autologous hemolymphopoietic stem cell (HSC) transplantation. It was postulated that the newly developing T cells might be tolerant to self antigens. The transfer of AID from affected donors to recipients of allogeneic HSC transplants has been reported for many organ-specific AID, including diabetes (IDDM), thyroiditis, myasthenia gravis and thrombocytopenic purpura (AITP); rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were not transferred. Conversely patients with the combination of AID and a severe blood disease (leukemia, aplasia) were cured of both diseases following allogeneic BMT, with the notable exception of a relapse in a patient with RA despite full donor engraftment. Allogeneic transplants are certainly more promising as far as concerns a resolution of AID, because they may also exert a graft-versus-autoimmunity effect by gradually eradicating the recipient's lymphopoiesis, but transplant related mortality (TRM) is considered still too high to employ this procedure consistently. New non-myeloablative conditioning regimens, designed to allow the donor's immune system to take over, are already utilized for malignant and non-malignant hematologic diseases, and may become an attractive option for severe, refractory AID. For the time being, however, autologous procedures are still safer, and are being utilized in many projects worldwide. The EBMT/EULAR Registry has collected over 70 patient reports. The more numerous and favorable results have been obtained up to now in multiple scleosis and in systemic lupus erythematosus; the worst in refractory autoimmune thrombocytopenic purpura. No definite conclusions as to the efficacy of autologous HSC transplantation, from marrow or from blood, with or without T-cell depletion, may be drawn at this time, but the feeling is that real cures will be very difficult to obtain by this approach, and that corticosteroid-free remissions and a general lowering of the autoimmune potential will be more realistic goals. Accurate comparisons with already existing aggressive immunosuppressive protocols will become necessary, if possible by means of prospective randomized clinical studies.
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PMID:Stem cell transplantation for severe autoimmune diseases: progress and problems. 979 58


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