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)

When experimental autoimmune encephalomyelitis (EAE) is induced by adoptive transfer of myelin basic protein (MBP)-specific lymphocytes the splenic noradrenergic and adrenocortical responses mirror in most respects those that occur following sensitization with spinal cord and Freund's adjuvant (CFA), despite the absence of the primary immune challenge. An early drop in splenic noradrenaline (NA), observed only when purified protein derivative-primed cells are transferred may reflect a vigorous proliferative response in vitro, not observed with MBP-specific cells. However, serum corticosterone (CS) levels and the density of splenocyte beta-adrenergic receptors were increased in both experimental groups within 3 days of cell inoculation. The stress of clinical signs of EAE resulted in highly significant increases in both splenic NA and plasma CS. Thus adoptively transferred EAE provides a well-delineated model of autoimmune disease for investigating the immunomodulatory role of the neural and endocrine systems.
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PMID:Splenic noradrenergic and adrenocortical responses during the preclinical and clinical stages of adoptively transferred experimental autoimmune encephalomyelitis (EAE). 168 80

Myelin basic protein (MBP) or helper T cells reactive against MBP induce an autoimmune disease, experimental allergic encephalomyelitis, in B10.PL and PL/J inbred mice. In both strains, virtually the entire repertoire of MBP-specific T cells recognize an N-terminal peptide fragment in the context of the I-Au molecule encoded by the major histocompatibility complex (MHC) and utilize a very limited set of T-cell receptor genes. To delineate the nature of the trimolecular complex, consisting of the T-cell receptor, MBP-peptide fragment, and MHC molecule (I-Au), we have synthesized 13 variants of the 9-mer N-terminal immunodominant peptide differing at residue 4 and studied their immune recognition in vitro and in vivo. These substitutions have a striking range of effects on T-cell activation, ability to bind to the MHC molecule, and initiation of immune responses in vivo. An understanding of the autoimmune peptide/MHC/T-cell receptor interactions allowed us to design variant 9-mer peptides that have high affinity for an MHC molecule and are effective in blocking experimental allergic encephalomyelitis, possibly through two distinct mechanisms, peripheral T-cell tolerance and the inhibition of binding of the encephalitogenic peptide to the MHC molecules.
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PMID:Amino acid variations at a single residue in an autoimmune peptide profoundly affect its properties: T-cell activation, major histocompatibility complex binding, and ability to block experimental allergic encephalomyelitis. 900 79

Susceptibility to experimental autoimmune encephalomyelitis (EAE), which is an autoimmune disease inducible by immunization with a brain-specific antigen in complete Freund's adjuvant (CFA), is different among strains. In an attempt to resolve the immune mechanisms by which the difference in susceptibility to EAE is regulated, we re-estimated susceptibility of several strains of rats, and the frequency of antigen-reactive T cells in each strain was determined by limiting-dilution analysis. EAE was induced in Lewis (LEW), PVG/c and BN rats using four different methods: (i) active immunization with guinea-pig myelin basic protein (GPBP) in CFA; (ii) immunization with GPBP in CFA that had been further supplemented with Mycobacterium tuberculosis H37Ra (supplemented CFA); (iii) adoptive transfer of GPBP-activated spleen cells into syngeneic rats; and (iv) transfer of a GPBP-specific T-cell line. The LEW strain was susceptible to all four methods. The PVG/c strain was resistant to immunization with GPBP in conventional CFA (GPBP/conv. CFA), but was susceptible to immunization with GPBP in supplemented CFA (GPBP/suppl. CFA) and to transfer of activated spleen cells. The BN strain was resistant to all methods. Limiting-dilution analysis using T cells from LEW, PVG/c or BN rats has revealed that each strain of rat displays a different pattern of frequencies of GPBP-reactive or the 68-88 sequence (GP68-88)-reactive T cells. LEW rats showed relatively high frequencies of GPBP-reactive and GP68-88-reactive T cells after immunization with either GPBP/conv. CFA or GPBP/suppl. CFA, symptomatic rats showing higher values than asymptomatic rats. In asymptomatic PVG/c rats, the frequency of GP68-88-reactive T cells was lower than that of GPBP-reactive T cells. In PVG/c rats with clinical EAE, however, GP68-88-reactive T cells increased in frequency and were almost the same as GPBP-reactive T cells. BN rats, on the other hand, responded very poorly not only to the GP68-88 sequence but also to the whole GPBP molecule, even after immunization with GPBP/suppl. CFA. These findings, obtained by limiting-dilution analysis, strongly suggest that the development of EAE in LEW, PVG/c and BN rats is closely related to the frequency of GPBP-reactive T cells. Furthermore, it is shown that resistance to EAE found in PVG/c and BN rats may be generated by different immune mechanisms.
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PMID:Limiting-dilution analysis of the frequency of myelin basic protein-reactive T cells in Lewis, PVG/c and BN rats. Implication for susceptibility to autoimmune encephalomyelitis. 168 93

Experimental allergic encephalomyelitis (EAE) is a model system for T cell-mediated autoimmune disease. Symptoms of EAE are similar to those of multiple sclerosis (MS) in humans. EAE is induced in susceptible animal strains by immunization with myelin basic protein (MBP) and potent adjuvant. The major T cell response to MBP in B10.PL mice is directed towards an NH2-terminal epitope and involves T cells expressing either V beta 8.2 or V beta 13 gene segments. Animals treated with a TCR V beta 8-specific mAb have a reduced incidence of EAE. We report here that the in vivo administration of a combination of anti-V beta 8.2 and anti-V beta 13 mAbs results in a long-term elimination of T cells involved in the response to MBP. When given before MBP immunization, anti-TCR antibody treatment leads to nearly complete protection against EAE. Antibody treatment also results in a dramatic reversal of paralysis in diseased animals. Thus, treatment with a combination of V beta-specific antibodies is a very effective therapy for the prevention and treatment of EAE. It is hoped that the future characterization of TCR V gene usage in human autoimmune diseases may lead to similar strategies of immune intervention.
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PMID:Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor V beta-specific antibodies. 169 55

Multiple sclerosis is thought to be an autoimmune disease of the central nervous system mediated by T cells specific for a myelin antigen. Myelin basic protein has been studied as a potential autoantigen in the disease because of its role as an encephalitogen in experimental autoimmune encephalomyelitis and post-viral encephalomyelitis and because of the presence in the blood of multiple sclerosis patients of in vivo-activated T cells reactive to myelin basic protein. Immune involvement in multiple sclerosis has been further suggested by the association with the major histocompatibility complex class II phenotype DR2, DQw1. To define the T-cell specificity toward myelin basic protein, 15,824 short-term T-cell lines were established from multiple sclerosis subjects, subjects with other neurological diseases, and normal controls. Here we report a higher frequency of T-cell lines reactive with a DR2-associated region of myelin basic protein between residues 84-102 in patients with multiple sclerosis compared with controls. A second region, identified between residues 143-168, was recognized equally in multiple sclerosis patients and controls and was associated with the DRw11 phenotype. These DR2 and DRw11 associations were also observed among T-cell lines generated from family members of a multiple sclerosis patient. The immunodominant 84-102 peptide from myelin basic protein was both DR2- and DQw1-restricted among different T-cell lines. These results raise the possibility that this immunodominant region may be encephalitogenic in some DR2+ individuals.
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PMID:T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. 169 70

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease. It is widely used as an animal model of multiple sclerosis (MS). We studied the prophylactic effects of FK 506 electrophysiologically and immunohistochemically in acute EAE. Female Lewis rats were sensitized with guinea pig spinal cord in complete Freund's adjuvant. FK 506 suspended in distilled water was orally administered at 1.0, 3.2, 5.0 or 10.0 mg/kg per day for 12 successive days starting from the day of sensitization. A placebo was used as the control. Administration of FK 506 at doses of 3.2 mg/kg per day and over significantly delayed the onset of clinical signs. However, the FK 506 group showed a relapse or a chronic state following the onset of EAE. We made a time course recording of cortical somatosensory evoked potential (cortical SEP: P 15). P 15 latency in the placebo group was significantly delayed in accordance with the clinical signs and showed immediate improvement upon recovery. Prolongation of P 15 latency in the FK 506 group also occurred concomitantly with the clinical signs, but the delay continued after the loss of symptoms as well. After the onset of EAE, the infiltrating lymphocyte subset was examined by the avidin-biotin peroxidase complex (ABC) method in the lumbar spinal cord. In the placebo group, the number of OX3+ (Ia) cells and the W 3 25+: OX8+ (helper/inducer T: suppressor/cytotoxic T) ratio clearly reflected the development and remission of EAE. In the FK 506 group, however, increases in OX8+ lymphocytes were observed irrespective of clinical sign fluctuation, and there were corresponding decreases in the W 3/25+: OX8+ ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of novel immunosuppressant FK 506 in acute experimental allergic encephalomyelitis]. 169 82

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease inducible in rodents by immunization of brain-specific antigens such as myelin basic protein (MBP). It is also well known that various strains of rats differ in their susceptibility to EAE upon active immunization. To elucidate the immune mechanisms of susceptibility and resistance to EAE, we first examined the T cell repertoire for MBP using thymectomized chimeras that possessed thymuses from EAE-susceptible (LEW) or EAE-resistant (BM) strains. It was revealed that T cell specificity of these chimeras was skewed toward that of the grafted thymus. Very interestingly, the chimeras bearing thymuses from the resistant strain developed severe EAE, keeping a hole in the encephalitogenic 68-88 sequence of MBP. These findings suggest that the strain-specific T cell repertoire itself is not involved in the regulation of EAE susceptibility. Furthermore, the analysis of the chimeras reconstituted with F1 T cells and marrow cells from various strains indicates that the major histocompatibility complex (MHC) molecules expressed on accessory cells primarily determine susceptibility or resistance to EAE. We finally showed, using various inbred and congenic rats carrying RT1l or RT1n, that susceptibility to EAE of rats carrying RT1l is heavily influenced by the background genes, whereas resistance to EAE of rats carrying RT1n is primarily regulated by the MHC molecules expressed on accessory cells without influence of the background genes.
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PMID:Analysis of the T cell repertoire for myelin basic protein in thymus-grafted and other types of chimera: evidence that major histocompatibility complex molecules on accessory cells rather than T cell specificity mainly regulate susceptibility to autoimmune encephalomyelitis. 169 40

To determine if the Ag that induces an autoimmune disease influences parental MHC haplotype molecule expression in situ in MHC heterozygotes, acute experimental allergic encephalomyelitis (EAE) was induced with different encephalitogenic peptides in (SJL/J x SWR)F1 mice. The mice were sensitized with either a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 103-116 YKTTICGKGLSATV which induces EAE in SWR (H-2q), but not SJL/J (H-2s) mice or a synthetic peptide corresponding to PLP residues 139-151 HCLGKWLGHPDKF which is encephalitogenic in SJL/J but not SWR mice. Mice were killed when they were moribund or at 30 days after sensitization. Twelve of 18 F1 mice given PLP peptide 103-116 and 12 of 17 mice given PLP peptide 139-151 developed EAE within 2 to 3 wk after sensitization. Cryostat sections of brain samples from F1 and parental mice were immunostained with a panel of mAb identifying H-2s and H-2q class I and II MHC molecules. In brains of controls, class I MHC molecules were expressed on choroid plexus, endothelial cells, and microglia whereas class II MHC molecules were absent. In EAE lesions, class I and II MHC molecules were present on inflammatory and parenchymal cells, but the degree of parental haplotype molecule expression did not vary with the different peptide Ag tested. Thus, in (SJL/J x SWR)F1 mice, myelin PLP peptides 103-116 and 139-151 are co-dominant Ag with respect to clinical and histologic disease and parental haplotype MHC molecule expression. We propose a unifying hypothesis consistent with these results and previous observations of differential Ia expression in (responder x non-responder)F1 guinea pigs. We suggest that MHC molecules may bind locally derived peptide Ag in inflammatory sites and that these interactions influence levels of MHC haplotype molecules on APC.
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PMID:Parental MHC molecule haplotype expression in (SJL/J x SWR)F1 mice with acute experimental allergic encephalomyelitis induced with two different synthetic peptides of myelin proteolipid protein. 170 6

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system mediated by T cells bearing TCR of restricted heterogeneity. Thus, in the murine PL strain, V beta-8.2 is used by 80% of the encephalitogenic T cells. This observation has led to the successful prevention and reversal of EAE by the in vivo use of mAb directed to these restricted gene products. In SJL mice, the V beta-17a gene product has been shown to be used by approximately 50% of encephalitogenic T cells subsequent to immunization with a myelin basic protein (MBP)-derived peptide. However, the other V beta genes used by encephalitogenic T cells in SJL EAE have remained uncharacterized. We now report, for the first time, the beta-chain-encoding DNA sequence of two encephalitogenic, MBP-reactive, SJL-derived T cell clones. These clones which are specific for H-2s and the carboxyl-terminus (amino acid 92-103) of MBP, use TCR encoded by V beta-4. In addition, we demonstrate that the transfer of EAE by a heterogenous SJL-derived encephalitogenic T cell line can be prevented using an anti-V beta-4 antibody in vivo. V beta-4 usage has been previously described in a H-2u/MBP amino-terminus-reactive encephalitogenic T cell. The present findings may thus further support the "V region-disease" hypothesis.
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PMID:Identification of encephalitogenic V beta-4-bearing T cells in SJL mice. Further evidence for the V region disease hypothesis? 170 84

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by inflammation and demyelination in the central nervous system. The effect of the immunosuppressive molecule transforming growth factor-beta, (TGF-beta 1) on chronic relapsing EAE produced by the transfer of myelin basic protein-specific T cell lines was studied. TGF-beta 1 markedly inhibited the activation and proliferation of myelin-basic protein-specific lymph node cells in vitro. This reduced the capacity of these cells to transfer EAE. In addition, administration of TGF-beta 1 in vivo consistently resulted in an improved clinical course, even when given during ongoing disease. Immunopathologic study demonstrated a marked reduction in central nervous system damage and expression of cell-surface lymphocyte function-associated Ag-1 and class II MHC molecules in TGF-beta 1-treated mice. These findings have identified TGF-beta 1 as a possible therapeutic agent for the human demyelinating disease multiple sclerosis.
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PMID:Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-beta 1. 170 29


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