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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelin basic protein (MBP)-specific T cell lines and clones have been established from rats of the major histocompatibility complex (MHC)-compatible Lewis and BS strains. All lines and clones are MHC class II restricted and share the CD4+ phenotype. The cells proliferate specifically in response to either a peptide representing amino acids #68-88 of guinea pig MBP, to residues #47-67 or to an unidentified myelin antigen which is distinct from MBP. All lines and clones specific for MBP express the same T cell receptor (TcR) variable (V) beta chain element, which is homologous to the mouse V beta 8.2 gene segment. Three lines/clones with the same antigen fine specificity have identical V beta D beta J beta junctions on the protein level, a region which represents part of the potential antigen-binding portion of the TcR; two of the lines express members of the V alpha 2 family. These results suggest biased usage of TcR V beta elements in rat T cells specific for MBP. Our findings broaden the basis for a rational therapeutic strategy to specifically intervene in the rodent model system of experimental allergic encephalomyelitis.
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PMID:T cell receptor beta chain usage in myelin basic protein-specific rat T lymphocytes. 246 13

T cell lines to myelin basic protein (MBP) developed following in vitro culture cause experimental allergic encephalomyelitis (EAE) upon transfer into naive recipient mice. We have, however, repeatedly observed that MBP-specific T cell lines lose their ability to transfer EAE after 40 days in culture. Analyses of such cell lines failed to show any differences in their proliferative responses to antigen, or in the secretion of interleukin-2 (IL-2) and/or IL-4 when compared to their encephalitogenic counterparts. In contrast, examinations of T cell receptor (TCR) beta-chain gene rearrangement patterns showed sequential changes in the clonal population of cells concomitant with the loss of encephalitogenic function. Furthermore, transfer of a non-encephalitogenic, genotypically altered cell line after long-term in vitro culture into mice challenged with MBP suppressed the development of EAE. These findings suggest that the development of such putative regulatory cells in vivo may be involved in the recovery in EAE.
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PMID:Spontaneous development in vitro of a myelin basic protein-specific suppressor T cell line. 247 59

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 mediated by CD4+ T cells reactive with myelin basic protein (MBP). Rats were rendered resistant to the induction of EAE by vaccination with synthetic peptides corresponding to idiotypic determinants of the beta chain VDJ region and J alpha regions of the T cell receptor (TCR) that are conserved among encephalitogenic T cells. These findings demonstrate the utility of TCR peptide vaccination for modulating the activity of autoreactive T cells and represent a general therapeutic approach for T cell-mediated pathogenesis.
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PMID:Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides. 281 89

In some susceptible mouse strains, intracerebral (IC) inoculation of Theiler's murine encephalomyelitis virus (TMEV) results in a persistent infection leading to chronic demyelinating disease. Previous genetic analyses between susceptible SJL/J and resistant C57BL/6 mice indicated a role for multiple unlinked genes in the development of clinical and histopathological disease, including a major influence of the D region of the H-2 complex. In this study, genetic analysis of a different strain combination (susceptible SJL/J and resistant BALB/c) also demonstrates the involvement of multiple genes, but the H-2 genotype (H-2s and H-2d, respectively) does not appear to contribute significantly to susceptibility differences. In both segregation studies and recombinant-inbred (R-I) analysis, clinical and histopathological disease occurs in both H-2s homozygotes and H-2d homozygotes (as well as H-2s/H-2d heterozygotes), with the actual frequency related to the proportion of non-H-2 genome from the susceptible strain. There appear to be at least two non-H-2 genes involved in differential susceptibility of SJL/J and BALB/c to TMEV-induced disease. Analysis of R-I strains generated from BALB/c and SJL/J progenitors indicates linkage of at least one of these non-H-2 genes to those encoding the constant portion of the beta-chain of the T cell receptor on chromosome 6. Many genes may actually be involved, but each strain comparison defines a different subset of these loci--only those at which the two strains in question carry "functionally" different alleles. Thus, different strain comparisons may accent the roles of different genes in resistance to the same infectious organism or disease process. In addition to the genes identified thus far, there may be yet other genes contributing to development of TMEV-induced disease, but their recognition may require analysis of still other strain combinations.
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PMID:Variations in genetic control of susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. I. Differences between susceptible SJL/J and resistant BALB/c strains map near the T cell beta-chain constant gene on chromosome 6. 302 79

Experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), is a paralytic disease of the central nervous system (CNS) mediated by T-lymphocytes reactive to myelin basic protein (MBP). Lewis rats actively immunized with fragment 68 to 82 of guinea pig MBP develop a monophasic disease with spontaneous recovery. Lymphocyte recognition of the primary encephalitogenic sequence of MBP (fragment 68 to 82) is V beta 8.2 T cell receptor (TCR) skewed [1-3]. Lewis rats in clinical remission at 1 month and 3 months after spontaneous resolution of EAE retain V beta 8.2 T-lymphocytes in the CNS when analyzed by reverse transcriptase polymerase chain reaction or in situ hybridization. In contrast, 1 and 3 months after clinical remission from syngeneic bone marrow transplantation, V beta 8.2 T lymphocytes are absent from the CNS. During clinically active EAE and inflammatory breakdown of the blood-brain barrier, immune ablation and reconstitution with syngeneic bone marrow results in clinical tolerance of the new immune system to myelin.
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PMID:Syngeneic bone marrow transplantation eliminates V beta 8.2 T lymphocytes from the spinal cord of Lewis rats with experimental allergic encephalomyelitis. 747 84

The molecular diversity of gamma delta T cells has not previously been investigated in experimental allergic encephalomyelitis (EAE). This study characterised the gamma delta T cell receptor (TCR) variable (V) region repertoires of T cells infiltrating the brains of EAE mice during development of the disease. TCR gamma- and delta-specific cDNAs were synthesised from total RNA prepared from brain samples and transcription of rearranged V genes was assessed by polymerase chain reaction amplification of TCR V-C transcripts and Southern blot analysis. In the early stages of EAE, the TCR gamma-chain repertoire consisted of V gamma 1-3 and V gamma 6 transcripts and, similarly, a few V delta transcripts that used primarily V delta 1, V delta 4 and V delta 5 gene segments were detected. During the progression of EAE, however, most V gamma and V delta TCR transcripts were observed in the brain. These results indicate that in the course of murine EAE there is an initial infiltration into the brain of a restricted population of gamma delta T cells followed by a heterogeneous gamma delta TCR repertoire as the disease develops. Moreover, the data suggest that gamma delta T cells may play a role in the pathogenesis of demyelinating autoimmune disease.
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PMID:Gamma delta T cell receptor variable region usage during the development of experimental allergic encephalomyelitis. 749 85

Encounters with antigen can stimulate T cells to become activated and proliferate, become nonresponsive to antigen, or to die. T cell death was shown to be a physiological response to interleukin-2-stimulated cell cycling and T cell receptor reengagement at high antigen doses. This feedback regulatory mechanism attenuates the immune response by deleting a portion of newly dividing, antigen-reactive T cells. This mechanism deleted autoreactive T cells and abrogated the clinical and pathological signs of autoimmune encephalomyelitis in mice after repetitive administration of myelin basic protein.
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PMID:T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis. 750 84

Models of T cell recognition suggest that amino acid residues in the CDR3 region of the T cell receptor (TCR) alpha or beta chain directly contact the major histocompatibility complex-bound peptide, and thus are crucial for providing peptide specificity. T cells derived from B10.PL or PL/J mice of H-2u haplotype, use only D beta 2 and J beta 2 gene segments in the recognition of the dominant determinant, Ac1-9/Au, of myelin basic protein (MBP). New Zealand White (NZW) mice, with identical class II H-2u genes (I-A and I-E), carry an 8.8-kb deletion in their TCR beta chain locus encompassing D beta 2 and J beta 2 gene segments. How does this deletion of the crucial D beta 2-J beta 2 region in NZW mice influence specific responses to Ac1-9/Au as well as to other known Au or Eu determinants of MBP? We found that these mice respond very poorly to the dominant Ac1-9/Au and to the subdominant 31-50/Eu determinant in in vitro proliferation assays as well as in their in vivo capacity to induce experimental autoimmune encephalomyelitis. This loss of response is apparently owing to the absence of high avidity TCRs with essential CDR3 residues contributed by D beta 2 or J beta 2 gene segments. These data reveal constraints in the recognition of certain antigenic structures, and further support a TCR-recognition model in which CDR3 residues of the TCR alpha and beta chains constitute the antigenic peptide-binding sites on the TCR molecule. Implications for autoimmune manifestations contributed by NZW genes in (NZB x NZW)F1 disease are also discussed.
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PMID:Holes in the T cell repertoire to myelin basic protein owing to the absence of the D beta 2-J beta 2 gene cluster: implications for T cell receptor recognition and autoimmunity. 751 12

In the present study, we have isolated and characterized five myelin basic protein (MBP)-reactive T cell lines directly from the brains of Lewis rats during the early paralytic phase of experimental autoimmune encephalomyelitis (EAE). Each T cell line responded to the dominant encephalitogenic epitope spanning residues 68-88, and did not react against the conserved encephalitogenic epitope [MBP(87-99)] or the nonencephalitogenic MBP epitope [MBP(50-69)]. We determined the T cell receptor (TcR) beta chain usage by polymerase chain reaction, DNA sequencing analysis and by generation of MBP-reactive hybridomas from one of the T cell lines (BT74). The results revealed that brain-infiltrating, MBP-reactive T cells freshly isolated early in the course of the disease exhibit TcR diversity.
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PMID:Characterization of brain-isolated rat encephalitogenic T cell lines. 751 12


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