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)

Previous experiments from this laboratory have shown that Lewis rats were protected from experimental allergic encephalomyelitis (EAE) induced by the injection of myelin basic protein (MBP) in Freund's complete adjuvant if they were treated with the encephalitogenic peptide of MBP covalently linked to mouse anti-rat immunoglobulin (Ig) D. It was suggested that this protection developed because the antibody-peptide conjugate targeted the peptide to B cells and that this mode of presentation induced a Th2-like T cell response that controlled the concomitant encephalitogenic Th1 reaction to the autoantigen. The current experiments were carried out to test this hypothesis and to examine the alternative explanation for the protective effect of the conjugate pretreatment, namely that it induced a state of nonresponsiveness in the autoantigenspecific T cells. It was shown that EAE induction was suppressed in Lewis rats when the antibody-peptide conjugate was injected intravenously 14 and 7 d before immunization with MBP in adjuvant, but that anti-MBP antibody titers were at least as high in these animals as in controls that were not pretreated with the conjugate before immunization. Lymph node cells from these pretreated animals, while proliferating in vitro to MBP as vigorously as those from controls, produced less interferon gamma and were very inferior in their ability to transfer disease after this in vitro activation. In contrast, these same lymph node cells from protected rats generated markedly increased levels of messenger RNA for interleukin (IL)-4 and IL-13. When these in vitro experiments were repeated using the encephalitogenic peptide rather than MBP as the stimulus, the proliferative response of lymph node cells from pretreated donors was less than that from controls but was still readily detectable in the majority of experiments. Furthermore, the cytokine expression induced by the peptide was similar to that elicited by whole MBP. While these results support the original hypothesis that the anti-IgD-peptide conjugate pretreatment protected rats from EAE by inducing a Th2-type cytokine response, a totally unexpected finding was that this pretreatment greatly reduced the level of leukocyte infiltration into the central nervous system. This result provides a direct explanation for the protective effect of the pretreatment, but it raises questions regarding migratory and homing patterns of leukocytes activated by different immunological stimuli.
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PMID:Prevention of experimental allergic encephalomyelitis in rats by targeting autoantigen to B cells: evidence that the protective mechanism depends on changes in the cytokine response and migratory properties of the autoantigen-specific T cells. 754 32

Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease if the central nervous system (CNS). Recently, the type I IFN, IFN-beta-1b was demonstrated to be a useful immunotherapy for MS. During treatment with IFN-beta-1b, toxicity at higher doses has been observed. IFN-tau, discovered for its role in the reproductive cycle, possesses all of the functions normally ascribed to the type I IFNs but lacks the toxicity normally associate with IFN treatment in vitro. We have examined the effects of IFN-tau treatment on experimental allergic encephalomyelitis (EAE), an animal model useful for the study of MS. EAE is a model of Ag-induced autoimmunity that can be modulated by bacterial superantigen to resemble the relapsing-remitting pattern of autoimmune disease observed in MS. IFN-tau was able to prevent development of EAE as effectively as IFN-beta but without associated toxicity such as lymphocyte suppression and weight loss. In addition, IFN-tau was able to prevent superantigen reactivation of EAE akin to the reduction in disease exacerbations observed in IFN-beta-1b treated MS patients. Mechanisms by which IFN-tau may prevent EAE include reduced proliferation in response to the autoantigen myelin basic protein and reduced TNF-alpha production. Thus, IFN-tau may prove to be a promising new IFN therapy for MS in light of its ability to prevent EAE and the lack of toxicity exhibited by this novel IFN.
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PMID:The IFN pregnancy recognition hormone IFN-tau blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity. 754 84

Recent advances in elucidating the activation and regulation of the autoimmune processes have provided new approaches for selective immunotherapy. Three different strategies are described: autoantigen-based therapy utilizing immunospecifically designed macromolecules and peptides, T-suppressor lines and clones, as well as antibodies specific to the antigen-MHC complex. These modalities, the efficacy of which has been demonstrated for experimental allergic encephalomyelitis, may be adapted to other experimental as well as human autoimmune diseases.
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PMID:Immunospecific drug design--prospects for treatment of autoimmune diseases. 758 81

Myelin/oligodendrocyte glycoprotein (MOG) is expressed specifically in the central nervous system (CNS) by myelinating glial cells, the oligodendrocytes. The external location of MOG on myelin sheaths and its late expression during myelinogenesis argue for a role of MOG in the completion of myelin and maintenance of its integrity. MOG is a target autoantigen in demyelinating diseases, such as experimental autoimmune encephalomyelitis (EAE) in animals and multiple sclerosis (MS) in humans. We previously located the gene encoding MOG to the major histocompatibility complex (MHC), both in human, by cytogenetics, and in mouse, by analysis of recombinants. To refine the position, we have now selected yeast artificial chromosome clones (YAC) which contain the MOG gene. Physical mapping of the human MOG and the mouse Mog genes by characterization of these YAC clones indicated that the gene is located at the distal end of the major histocompatibility complex (MHC) class Ib region in both species. The human MOG gene lies 60 kilobases (kb) telomeric to HLA-F in a head-to-head orientation; the mouse Mog gene lies 25 (kb) telomeric to H2-M5 in a tail-to-head orientation. These orthologous genes provide markers for comparative analysis of the evolution of the MHC in the two species. The physical mapping of MOG should facilitate analysis of its role in hereditary neurological diseases, and the YAC clones identified here will permit the identification of new genes in the region.
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PMID:Physical mapping of the human and mouse MOG gene at the distal end of the MHC class Ib region. 759 Sep 72

Both heterogeneity and restricted heterogeneity of the encephalitogenic myelin basic protein (MBP) peptide-specific T cell receptors (TCRs) were demonstrated in inbred animals depending on the strain-specific genetic characteristics, the stage of the disease, the compartment of the lymphocytes obtained and the methodology used. Nevertheless, the similar features of some MBP-specific TCRs demonstrated across species suggest that conservation of these autoantigen-specific molecules undoubtedly exists, even though the degree of this conservation is controversial. However, the unequivocal heterogeneity of the immune response directed at one of the most important myelin constituents, proteolipid lipoprotein (PLP), which occurs either as a primary or a secondary event during experimental allergic encephalomyelitis (EAE), indicates the complexity of the in vivo situation. Intramolecular and intermolecular spreading of antigen specificity during the course of the disease indicates that a TCR directed therapy may not be the choice of intervention in established disease even in individual strains of laboratory animals with restricted heterogeneity of the primary MBP-specific response. Studying the sequence of events, the recruited regulatory cells and cytokines, and the stromal factors controlling persistence or death of activated, memory cells in the tissue lesion, may reveal new therapeutic modalities with more universal applicabilities.
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PMID:Characteristics of the T lymphocytes involved in experimental allergic encephalomyelitis. 759 46

Predominant usage of V beta 8.2 gene segments, encoding a T-cell receptor (TCR) beta chain variable region, has been reported for pathogenic Lewis rat T cells reactive to myelin basic protein (MBP). However, up to 75% of the alpha/beta T cells in a panel of MBP-specific T-cell lines did not display TCR V beta 8.2, V beta 8.5, V beta 10, or V beta 16 elements. To further investigate TCR usage, we sorted the T-cell lines for V beta 8.2- and V beta 10-positive T cells or depleted the lines of cells with these TCRs. V beta 8.2-positive T cells and one of the depleted T-cell lines strongly reacted against the MBP peptide MBP-(68-88). The depleted T-cell line caused marked experimental autoimmune encephalomyelitis (EAE) even in Lewis rats in which endogenous V beta 8.2-positive T cells had been eliminated by neonatal treatment with anti-V beta 8.2 monoclonal antibodies. T-cell hybridomas generated from this line predominantly used V beta 3 TCR genes coexpressed with TCR V alpha 2 transcripts, which were also used by V beta 8.2-positive T cells. Furthermore, V beta 10-positive T cells reactive to MBP-(44-67) were encephalitogenic when injected immediately after positive selection. After induction of EAE by sorted V beta 8.2- or V beta 10-positive T-cell lines, immunocytochemical analysis of the spinal cord tissue showed a predominance of the injected TCR or of nontypable alpha/beta T cells after injection of the depleted line. Our results demonstrate heterogeneity of TCR beta-chain usage even for a single autoantigen in an inbred strain. Moreover, V beta 8.2-positive T cells are not essential for the induction and progression of adoptive-transfer EAE.
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PMID:T-cell receptor (TCR) usage in Lewis rat experimental autoimmune encephalomyelitis: TCR beta-chain-variable-region V beta 8.2-positive T cells are not essential for induction and course of disease. 759 40

The potential role of certain important immunoregulatory and effector cytokines in autoimmune neuroinflammation have been studied. We have examined the expression of mRNA, with in situ hybridization, of interferon gamma (IFN-gamma), interleukin 4 (IL-4) and transforming growth factor beta (TGF-beta) both in sections of spinal cords and the antigen-induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63-88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords, the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4. Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63-88 induced lymphoid cells to TGF-beta production. Thus, an autoantigen-specific production of TGF-beta occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive autoimmunity systemically.
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PMID:Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells. 760 12

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system. It is mediated by T cells and is an animal model for the human disease multiple sclerosis. In most mouse strains that are susceptible to induction of EAE by myelin basic protein, a dominant peptide of myelin basic protein is recognized by encephalitogenic T cells. We report here the susceptibility of the A.CA strain (H-2f) to myelin basic protein induced EAE and that multiple peptides of myelin basic protein (1-11, 9-20, and 87-99) can induce disease in these mice. The finding that multiple epitopes of the same self-antigen can elicit EAE in an inbred strain of mouse raises the possibility of more heterogeneity in encephalitogenic peptides of the putative autoantigen in human disease than previous studies have suggested.
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PMID:Multiple encephalitogenic peptides of myelin basic protein in A.CA mice. 768 Sep 64

Experimental allergic encephalomyelitis (EAE) is considered the animal disease model for multiple sclerosis (MS) in humans. However, EAE is an acute disease whereas MS is a chronic disease. The on-off nature in both diseases of autoimmune reactivity suggests a regulatory response by the host, a response which can effect the autoreactive T cell by modulating-up or modulating-down. This review discusses various aspects of this regulation, seen after administration of autoantigen, of antibody directed at the T cell receptor (TcR), and of fragments of the TcR itself.
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PMID:The ups and downs of EAE. 768 9

On the hypothesis that myelin basic protein isolated with surrounding lipids may constitute an autoantigen in demyelinating diseases, we studied the antibody response to the lipid-free and lipid-bound form of myelin basic protein during the course of experimental autoimmune encephalomyelitis induced in rats with either form of protein. Immunization with the lipid-bound form of myelin basic protein induced high titres of antibodies directed to the protein, accompanied by no antibodies to cerebroside 30 days after immunization. Antibodies specifically directed to the lipid-bound form of myelin basic protein were revealed after removal of antibodies recognizing the delipidated myelin basic protein. Anti lipid-bound myelin basic protein antibodies could already be detected at day 10 post-immunization, reaching a maximum at day 20 post-immunization. Demonstrations of antibodies entirely specific for the lipid-bound form of myelin basic protein suggests that this molecule may present epitopes not to be found in its already extensively studied primary structure, possibly the result of conformational changes following lipid binding.
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PMID:Antibodies specific for the lipid-bound form of myelin basic protein during experimental autoimmune encephalomyelitis. 768 1


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