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)

Experimental allergic encephalomyelitis (EAE) is a model of antigen-specific T cell-mediated autoimmune disease. The alpha-acetylated, NH2-terminal nine amino acids (1-9NAc) of myelin basic protein (MBP) represents the dominant T cell epitope for the induction of EAE in the B10.PL (H-2u) strain. We tolerized neonatal B10.PL mice to 1-9NAc and studied the proliferative responses to this peptide and to whole MBP. Mice exposed to 1-9NAc in the neonatal period were tolerant to subsequent challenge at the proliferative T cell level. Similarly, in the 1-9NAc-tolerant group, both the incidence and severity of 1-9NAc induced EAE were greatly reduced. The fact that we were able to tolerize mice normally responsive to MBP suggests that this self antigen is sequestered (within the central nervous system) and hence tolerance to it is not normally induced. No significant difference in disease incidence was seen in response to rat MBP between control animals and 1-9NAc-tolerized mice (50% in both groups), demonstrating the presence of at least one additional encephalitogenic determinant elsewhere on the molecule. We have successfully prevented disease induction by peptide-induced tolerization. Tolerance induction by peptides provides a new and specific strategy in the prevention of autoimmunity. However, it will be clearly necessary to fully define all epitopes potentially capable of inducing pathogenic T cells to ensure complete and effective therapy of T cell-mediated autoimmune disease.
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PMID:Peptide-specific prevention of experimental allergic encephalomyelitis. Neonatal tolerance induced to the dominant T cell determinant of myelin basic protein. 246 64

A feature common to many animal models of autoimmune disease, for example, experimental allergic encephalomyelitis, experimental autoimmune myasthenia gravis and collagen-induced arthritis, is the presence of self-reactive T cells in healthy animals, which are activated to produce disease by immunization with exogenous antigen. It is unclear why these T cells are not deleted during ontogeny in the thymus and, having escaped tolerance induction, why they are not spontaneously activated by self-antigen. To investigate these questions, we have examined an experimental model in which mice are tolerant to an antigen despite the presence of antigen-reactive T cells. We find that the T cells that escape tolerance induction are specific for minor determinants on the antigen. We propose that these T cells evade tolerance induction because some minor determinants are only available in relatively low amounts after in vivo processing of the whole antigen. For the same reason, these T cells are not normally activated but can be stimulated under special circumstances to circumvent tolerance.
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PMID:How some T cells escape tolerance induction. 247 88

Two synthetic immunodominant and nonencephalitogenic peptides of myelin basic protein, N1-20 and AcN9-20, effectively compete with an encephalitogenic peptide, AcN1-11, in an in vitro T-cell response restricted by class II major histocompatibility complex products (I-Au). These mutant peptide constructs, which do not occur in nature, also compete with the self-antigen for the in vivo induction of T cells primed with the encephalitogen AcN1-11. By using these nonpathogenic competitor peptides, it is possible to prevent the development of a prototypic T-cell-mediated autoimmune disease, experimental allergic encephalomyelitis. These results suggest possibilities for the utilization of competitor peptides for therapy of T-cell-mediated autoimmune diseases linked to specific major histocompatibility complex genes.
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PMID:Prevention of experimental encephalomyelitis with peptides that block interaction of T cells with major histocompatibility complex proteins. 248 Jun 2

The optimal form of treatment for an autoimmune disease should be highly specific, have few side effects, and allow treatment of clinically apparent disease. One target that could fulfill these requirements is the T cell receptor. To answer the question whether treatment of autoimmune disease is possible with anti-T cell receptor antibodies, the heterogeneity of T cell receptor elements utilized in the T cell mediated autoimmune disease experimental allergic encephalomyelitis was analyzed. The limited heterogeneity of these elements allowed prevention and treatment of clinical autoimmune disease with anti-T cell receptor monoclonal antibodies. These results and their potential value for other autoimmune diseases are discussed.
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PMID:T cell receptors in autoimmune disease as targets for immune intervention. 248 95

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS). Its immune mechanism is well understood at the cellular and molecular levels, which is herein reviewed. Susceptibility to EAE is under the control of the genes partially inside and partially outside the H-2 complex. There are two myelin constituents known to be encephalitogenic, myelin basic protein and proteolipid apoprotein. EAE is mediated by effector T cells sensitized to the encephalitogen. Effector T cells bear surface phenotypes of Lyt1+2-, L3T4+, and they are activated by the encephalitogen/self Ia complex or certain alloantigens and acquire encephalitogenic activity. By unknown homing mechanisms, the effector T cells invade the CNS and induce the target phase phenomena, which include Ia-antigen expression in the local tissue, activation of procoagulant activity, breakdown of the blood-brain barrier, and excretion of lymphokines which induce inflammation and demyelination, resulting in functional alteration. Possibility of specific immune therapy is postulated as a model for human autoimmune disease.
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PMID:Cellular and molecular aspects of the pathomechanism and therapy of murine experimental allergic encephalomyelitis. 248 1

Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals.
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PMID:Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras. 252 17

Acute experimental allergic encephalomyelitis (EAE) in the Lewis rat is a cell-mediated autoimmune disease of central nervous system myelin. The lesion has been characterized by breakdown of the blood-brain barrier, edema, and periventricular infiltration of macrophages and lymphocytes. At the early stage of the disease, the astrocytes show a marked increase in immunostaining for glial fibrillary acidic protein (GFAP). A corresponding increase in GFAP content, however, cannot be demonstrated. Electron microscopic examination of the early lesion shows a typical reactive astrocytic response expressed by an enlarged watery cytoplasm, particularly at the level of the processes surrounding neurons and blood vessels and in the neuropil itself. The astroglial processes contain numerous glycogen particles (aggregates and single particles). Glial filaments are also conspicuous and are arranged in small bundles or loose thin filaments adjacent to the bundles. The glial filaments that normally appear as tight bundles have expanded and appear less dense. We suggest that the increase in GFAP immunostaining of the astrocytes in the early lesion is due in part to edema, which causes dissociation of the filaments and thereby exposes more antigenic sites to the antibodies.
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PMID:Dissociation of GFAP intermediate filaments in EAE: observations in the lumbar spinal cord. 253 Jan 71

Experimental allergic encephalomyelitis (EAE) in Lewis rats is an acute, monophasic autoimmune disease, and rats recovering from EAE are generally resistant to active reinduction. However, following immunosuppression with a high dose (100-200 mg/kg) of cyclophosphamide (CY), EAE was reinduced in convalescent rats, irrespective of whether or not they were rechallenged with the encephalitogenic inoculum. Reinduction of EAE was not observed in rats treated with low doses (20 mg/kg or less) of CY. A selective inhibition of suppressor cells during the convalescent stage may be responsible for the reinduction of EAE in Lewis rats.
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PMID:Reinduction of experimental allergic encephalomyelitis in convalescent Lewis rats with cyclophosphamide. 258 Sep 57

We characterized the effector cells which mediate experimental autoimmune encephalomyelitis (EAE) on the basis of selective adherence properties. Nylon-nonadherent spleen cells (SpC) from Lewis rats challenged earlier with myelin basic protein (BP) in adjuvant were separated by 'panning' on Petri dishes coated with monoclonal antibody (MAb) OX22. OX22 recognizes high molecular weight forms of the leukocyte-common antigen which is present on several cell types, including the CD4-positive T cells which mediate delayed hypersensitivity reactions. We found that the EAE effector cells were enriched in the OX22-adherent T cell population, which supports the hypothesis that delayed hypersensitivity is important in the pathogenesis of this autoimmune disease.
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PMID:Effector cells of autoimmune encephalomyelitis in the rat belong to the CD4-positive, OX22-adherent T cell subset. 258 91

The transforming growth factors TGF-beta 1 and beta 2 are cytokines with pronounced effects on leukocyte growth and function. To evaluate a potential use of these factors as immunosuppressive agents, we compared the effects of TGF-beta 1 and beta 2 on autoimmune T cells in rat inflammatory central nervous system disease, experimental allergic encephalomyelitis (EAE). We observed that both factors strongly inhibited in vitro activation of autoimmune T cells, suppressed the accumulation of interleukin-2 mRNA and decreased the expression of rat T cell activation antigens. In addition, cyclical changes in susceptibility to TGF-beta was observed with T line cells. The modulation of in vitro T cell function is associated with a considerable suppression of encephalitogenic capacity of autoimmune T line cells. Thus, TGF-beta 1 and beta 2 might have physiologic importance in limiting local T lymphocyte proliferation and effector function in autoimmune disease.
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PMID:Transforming growth factors beta 1 and beta 2: cytokines with identical immunosuppressive effects and a potential role in the regulation of autoimmune T cell function. 280 92


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