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

Inoculation of Lewis rats with live or attenuated (irradiated or paraformaldehyde-fixed) CD4+ encephalitogenic T cells (S1 line) protects the recipients from transferred experimental autoimmune encephalomyelitis (tEAE) induced by S1 cells. A CD8+ T lymphocyte population specifically activated against the EAE-inducing S1 cells can be readily isolated from the lymphoid organs of pretreated animals. We show, in the present study, that encephalitogenic T cell lines derived from Lewis rats differ in their ability to induce resistance against tEAE in vivo and to stimulate CD8+ cell proliferation in vitro. We also demonstrate that the S19 line of encephalitogenic T cells, in combination with myelin basic protein (MBP), can stimulate CD8+ cell proliferation in vitro. The CD8+ cells generated in this way strongly suppress MBP-specific T cell proliferation in vitro. This combined effect of T cells and MBP was also evident in vivo. Neither S19 cells nor MBP alone induced resistance against S19-mediated tEAE, rather coinjection of these cells and MBP was required. Our results suggest that resistance to EAE is mediated by distinct populations of encephalitogenic T cells that activate Ts cells through different mechanisms. In some instances, both autoreactive T cells and their relevant autoantigen(s) may be needed to activate Ts cells in vivo.
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PMID:Functional heterogeneity among CD4+ encephalitogenic T cells in recruitment of CD8+ T cells in experimental autoimmune encephalomyelitis. 247 27

Multiple sclerosis is a demyelinating disease of the central nervous system with genetic, viral and autoimmune characteristics. Myelin basic protein (MBP) is a suspected target autoantigen since it induces experimental autoimmune encephalomyelitis, an animal model closely resembling multiple sclerosis. The disease is mediated by Class II restricted, MBP-reactive T cells possessing the T helper/inducer phenotype. In the present study, we have isolated MBP-reactive T cell clones from the peripheral blood of a chronic progressive multiple sclerosis patient. The clones displayed blastogenic memory responses when rechallenged with the autoantigen and irradiated autologous lymphocytes. MBP recognition by the autoantigen-reactive T lymphocytes was restricted by major histocompatibility complex Class II antigens. Both CD4+8- and CD4-8+ MBP-reactive T cell clones were obtained.
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PMID:MHC-restricted autoantigen-reactive T cell clones in multiple sclerosis. 248 13

T-lymphocytes recognize antigen in a trimolecular complex: The T-cell receptor binds to a processed fragment of antigen that itself is bound to a major histocompatibility complex (MHC) molecule on the surface of an antigen-presenting cell. The trimolecular complex controls antigen-specific T-cell activation in normal and abnormal immune reactions. Recent progress in myasthenia gravis (MG) and experimental autoimmune encephalomyelitis (EAE) exemplifies this, leading to the following conclusions: (1) Autoimmune T cells may act by interfering with immunoregulation (as in MG) or by directly mediating autoimmune damage (as in EAE), or both. (2) In both diseases, the autoimmune T cells are clonally heterogeneous but recognize only a limited number of epitopes on the autoantigen (acetylcholine receptor in MG; myelin basic protein in EAE). Many of these epitopes can be defined as short peptide fragments of antigen, bound to a particular type of MHC molecule. (3) The MHC determines which peptides are recognized by autoimmune T cells in a given patient or inbred animal strain. (4) The discovery of the limited repertoire of autoimmune T cells has allowed considerable progress in the immunotherapy of EAE, using either monoclonal antibodies or cytotoxic T cells directed against clonotypic determinants on the autoaggressive T cells. (5) One obstacle to this approach in human disease is the polymorphism of the MHC in the species and the commensurate heterogeneity of autoimmune T cells.
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PMID:Neurological autoimmune disease and the trimolecular complex of T-lymphocytes. 266 95

A synthetic copolymer of amino acids, copolymer 1 (Cop 1), proved to be very effective in suppressing experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). It is 1 of a series of synthetic amino acid copolymers which simulate the basic protein constituent of the myelin sheath and the autoantigen responsible for induction of EAE. It cannot induce EAE but it does suppress it in a variety of animals. The immunological cross-reaction between Cop 1 and the basic protein is the basis for this suppressive activity. In view of the resemblance between EAE and MS, clinical trials with Cop 1 in MS were started. The first preliminary clinical trial was at this hospital and involved 4 patients with severe MS. A double-blind, randomized placebo-controlled pilot trial was carried on for 2 years in 50 patients with the exacerbating-remitting form of MS but with a Kurtzke Disability Status Scale rating of no more than 6. There were statistically significant differences in the number of patients with exacerbations in the placebo group, 23, as compared to only 16 in the Cop 1-treated group. As to exacerbations per patient, the 2-year averages were 2.7 and 0.6, respectively. Side-effects of Cop 1 were minimal. These results suggest that Cop 1 may be beneficial when given early in the exacerbating-remitting form of MS. Further trials, necessary to establish its efficacy in MS, are being run at the Albert Einstein College of Medicine in NY.
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PMID:[Clinical trial of copolymer 1 in multiple sclerosis]. 268 Aug 16

mAb reactive with T suppressor factors (TsF) were used to alter the course of myelin basic protein-induced experimental allergic encephalomyelitis in (SJL/J x PL/J)F1 mice. In vivo administration of mAb 14-12, reactive with effector TsF, exacerbated the clinical expression of encephalomyelitis as evidenced by prolonged periods of total limb paralysis in affected animals. This aggravation of disease signs is probably related to the inhibition of effector Ts function by mAb 14-12 thus allowing T cell autoreactivity to proceed unchecked. Disease course was influenced more favorably by i.v. administration of mAb 14-30 reactive with a subset of inducer TsF. Ten days of treatment with this mAb resulted in a reduction in the incidence and severity of disease, noted as the development of minimal limb weakness but no paralysis in the majority of affected animals. Adoptive transfer experiments revealed the presence of Ag-specific Ts in mAb 14-30-treated mice that inhibited recipient Lyt-1+ responses to myelin basic protein, the immunizing autoantigen. Suppression by transferred Ts was revealed only by treatment of the donor population with anti-Lyt-1.2 plus C, however, indicating a role for contrasuppressor activity in the regulation of autoimmune T cell function. Results are considered relevant to the potential for immunotherapeutic management of multiple sclerosis in man.
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PMID:Modulation of experimental allergic encephalomyelitis with anti-T suppressor factor antibodies. 290 41

Down-regulatory phenomena have been described in several experimental models of tissue-specific, T-cell-mediated autoimmunity. For example, resistance to active induction of experimental autoimmune encephalomyelitis (EAE) can be induced by pretreating animals with non-pathogenic inocula of autoantigen or effector cells. Moreover, animals that have recovered from one EAE episode are resistant to subsequent induction of EAE. In some models, resistance to EAE has been transferred with immune cells to naive recipients. These experiments, which were based on transfers of unseparated immune cell populations, are difficult to interpret. Immune suppression circuits are known to be complex and involve various distinct cellular subsets. To further complicate the issue, resistance to EAE can be transferred not only by suppressor cells, but also by encephalitogenic effector cells injected in 'subclinical' doses. We describe now the isolation of homogeneous T lymphocyte lines from the spleens of Lewis rats that had recovered from T-cell-mediated EAE (tEAE) caused by the MBP-specific T cell line S1. These spleen-derived T line cells express the CD8 phenotype and specifically respond to determinants on the inducing S1 line, but not to the autoantigen MBP. Furthermore, the anti-S1 cells selectively lyse the encephalitogenic S1 T line in vitro and efficiently neutralize their encephalitogenic capacity in vivo.
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PMID:Suppression of experimentally induced autoimmune encephalomyelitis by cytolytic T-T cell interactions. 296 94

The central role of T lymphocytes in the initiation, regulation and propagation of autoimmune diseases defines them as most suitable targets for selective immunotherapy. The recent advance in culturing human and animal T cell lines allows us to select monoclonal antibodies specific for differentiation antigens expressed by activated T lymphocytes. We selected a monoclonal antibody cytotoxic for a subpopulation of activated rat T cells. In vivo, this antibody effectively blocks immune responses to foreign antigens or autoantigen and prevents development of autoimmune diseases like experimental allergic encephalomyelitis and adjuvant arthritis. Even already established disease can be blocked by a single injection of antibody. Furthermore, this monoclonal antibody can be used to monitor the course of autoimmune disease progression from peripheral blood samples.
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PMID:Therapy of rat autoimmune disease by a monoclonal antibody specific for T lymphoblasts. 349 Nov 49

The factors contributing to chronic relapsing inflammatory disease processes of the central nervous system (CNS) and demyelination are poorly understood. In addition to cellular immune reactions, humoral factors such as antibodies might quantitatively or qualitatively influence the disease process. We therefore investigated the effects of administration of a monoclonal antibody specific for a CNS autoantigen on both acute and chronic experimental autoimmune encephalomyelitis (EAE) in mice and rats. This monoclonal antibody, 8-18C5, specific for a myelin/oligodendrocyte glycoprotein, was observed to accelerate clinical and pathologic changes of CNS autoimmune disease. In SJL mice with chronic relapsing EAE, injection of antibody into animals recovering from an attack induced fatal relapses; in Lewis rats, acute EAE was enhanced and associated with a hyperacute inflammatory response with demyelination, a feature not commonly seen in acute EAE. The demonstration that relapses and demyelination can be induced by administration of a white matter-reactive monoclonal antibody offers new possibilities to study processes resulting in CNS damage during autoimmune disease. Furthermore, these findings support the immunopathogenic potential of antibody to myelin components in inflammatory CNS disease processes and, specifically, in causing demyelination.
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PMID:A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. 350 Sep 78

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

Retinal S antigen is a potent autoantigen used for the induction of experimental allergic uveoretinitis (EAU). EAU is an organ-specific disease and shows many similarities to other autoimmune diseases such as experimental encephalomyelitis. This paper describes the preparation of highly purified S antigen by using a one-step ion-exchange method. High yields of the protein were obtained. S antigen prepared by this method induces a prolonged posterior uveoretinitis with cellular infiltration in the vitreous and specific loss of retinal photoreceptor cells. The purity of the protein was checked by silver-stained SDS-polyacrylamide gels and immunoblotting techniques.
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PMID:A simplified method for the isolation of highly purified bovine retinal S antigen. 380 62


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