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)

Copolymer 1 (Cop 1) is a synthetic basic random copolymer of amino acids that has been shown to be effective in suppression of experimental allergic encephalomyelitis and has been proposed as a candidate drug for multiple sclerosis. Cop 1 is immunologically cross reactive with myelin basic protein (BP) and was shown to inhibit murine BP-specific T-cell lines of various H-2 restrictions. In the present study these findings were extended to include human T-cell lines. Cop 1 competitively inhibited the proliferative responses and interleukin 2 secretion of six BP-specific T-cell lines and 13 clones with several DR restrictions and epitope specificities. Conversely, BP inhibited--albeit to a lesser extent--the response of all the Cop 1-specific T-cell lines and clones, irrespective of their DR restrictions. Another random copolymer of tyrosine, glutamic acid, and alanine, denoted TGA, had no effect on these lines. Neither Cop 1 nor BP inhibited the response of lines and clones specific for purified protein derivative. Cop 1 and BP exerted their cross-inhibitory effects only in the presence of antigen-presenting cells. These results suggest that Cop 1 can compete with BP for the binding to human major histocompatibility complex molecules. In view of recent studies implicating BP reactivity in multiple sclerosis, these findings suggest a possible mechanism for the beneficial effect of Cop 1 in this disease.
 ...
PMID:Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic protein. 137 Mar 47

Copolymer-1 (Cop-1) has been shown to inhibit in vivo development of experimental allergic encephalomyelitis (EAE) in animals and has been reported to have some therapeutic benefit in relapsing/remitting multiple sclerosis (MS). The mechanism by which Cop-1 acts in vivo is not known. The present study demonstrates that Cop-1 inhibits the in vitro response of several antigen-specific murine T cell hybridomas restricted to I-A, and to a lesser extent, I-E. The ability of human myelin basic protein (MBP)-specific T cell lines (TCL) to lyse targets in the context of three HLA-DR types associated with MS was also impaired by Cop-1. The results suggest that the observed inhibition was due to competition between Cop-1 and nominal antigen for the class II major histocompatibility complex (MHC) peptide binding site.
 ...
PMID:Copolymer-1-induced inhibition of antigen-specific T cell activation: interference with antigen presentation. 137 32

Theiler's murine encephalomyelitis virus is responsible for a chronic inflammatory demyelinating disease of the central nervous system of the mouse. The disease is associated with persistent viral infection of the spinal cord. Some strains of mice are susceptible to viral infection, and other strains are resistant. The effect of the genetic background of the host on viral persistence has not been thoroughly investigated. We studied the amount of viral RNA in the spinal cords of 17 inbred strains of mice and their F1 crosses with the SJL/J strain and observed a large degree of variability among strains. The pattern of viral persistence among mouse strains could be explained by the interaction of two loci. One locus is localized in the H-2D region of the major histocompatibility complex, whereas the other locus is outside this complex and is not linked to the Tcrb locus on chromosome 6.
 ...
PMID:The interaction of two groups of murine genes determines the persistence of Theiler's virus in the central nervous system. 137 8

The minimum structural requirements for peptide interactions with major histocompatibility complex (MHC) class II molecules and with T cell receptors (TCRs) were examined. In this report we show that substituting alanines at all but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not alter its ability to bind A alpha uA beta u (MHC class II molecules), to stimulate specific T cells and, surprisingly, to induce experimental autoimmune encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice. Most other amino acid side chains in the Ac1-11 peptide are essentially irrelevant for T cell stimulation and for disease induction. Further analysis revealed that binding to A alpha uA beta u occurred with a peptide that consists mainly of alanines and only three of the original residues of Ac1-11. Moreover, when used as a coimmunogen with MBP Ac1-11, this peptide inhibited EAE. The finding that a specific in vivo response can be generated by a peptide containing only five native residues provides evidence that disease-inducing TCRs recognize only a very short sequence of the MHC-bound peptide.
 ...
PMID:A polyalanine peptide with only five native myelin basic protein residues induces autoimmune encephalomyelitis. 138 66

Peptide analogues of disease-associated epitopes were studied for inhibition of experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rats. EAE- and AA-associated analogues were selected as competitors because of their in vitro inhibitory activity on proliferation of encephalitogenic and arthritogenic T cells. Although the EAE-associated competitor had a superior major histocompatibility complex (MHC) binding affinity, the AA-associated competitor was a better inhibitor of the in vitro proliferation of arthritogenic T cells. Furthermore, although in vivo EAE was inhibited by both competitors, AA was only inhibited by the AA-associated competitor. Remarkably, in contrast to what was expected of a regular MHC competitor peptide, the AA-associated peptide analogue also prevented AA upon immunization before disease induction and appeared to induce T cell responses that crossreacted with the original disease-associated epitope. Therefore, it is concluded that antigen-specific regulatory mechanisms were involved in synergy with MHC competition. The integration of both qualities into a single "competitor-modulator" analogue peptide may lead to the development of novel, more effective, disease-specific immunomodulatory peptides.
 ...
PMID:Disease inhibition by major histocompatibility complex binding peptide analogues of disease-associated epitopes: more than blocking alone. 138 Sep 74

Cells that express major histocompatibility complex (MHC) class II molecules can interact directly with CD4 T lymphocytes and either activate immune reactions or become the targets of T-cell-mediated cytotoxic attack. Using rat optic nerve cultures combined with immunocytochemistry and in situ hybridization, we have shown that oligodendrocytes, the major myelin-forming cells of the central nervous system and the main casualty of the immune attacks associated with multiple sclerosis and experimental allergic encephalomyelitis, can be readily induced to express MHC class II mRNA and surface antigens in vitro by exposure to gamma interferon, provided the glucocorticoid dexamethasone is included in the culture medium. Oligodendrocytes exposed to gamma interferon without dexamethasone fail to express MHC class II molecules, which may account for the failure of previous attempts to induce expression in these cells. In the experiments reported here MHC class II expression can be demonstrated both on galactocerebroside-positive cells and on mature oligodendrocytes that express proteolipid protein. These findings expand possibilities for understanding immune-related oligodendrocyte killing and demyelination in human and experimental demyelinating diseases.
 ...
PMID:In the presence of dexamethasone, gamma interferon induces rat oligodendrocytes to express major histocompatibility complex class II molecules. 140 2

Chronic infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in central nervous system (CNS) demyelination similar to multiple sclerosis. Demyelination induced by TMEV is mediated, in part, by class I-restricted CD8+ T lymphocytes. For these T cells to function, they must recognize virus-infected CNS targets in the presence of class I major histocompatibility complex (MHC) antigen. Therefore, we studied in vivo expression of class I MHC antigen and viral antigen-RNA in prototypic mouse strains that are susceptible (SJL/J) or resistant (C57BL/10SNJ) to TMEV-induced demyelination. In brains of resistant mice, viral antigen-RNA expression peaked on day 3 after infection and was effectively diminished by day 5 such that few virus-infected cells were ever detected in the spinal cord. In contrast, susceptible mice demonstrated delay in clearance of TMEV from the brain and a subsequent increase and persistence of viral antigen-RNA in the spinal cord for as long as 277 days. Viral infection resulted in "upregulation" of class I MHC expression in the CNS. Class I MHC antigens were expressed as early as 1 day after infection in the choroid plexus of both strains of mice before detection of viral antigen or inflammation. In resistant mice, class I MHC expression predominated in the gray matter of the brain and spinal cord on day 7 after infection but returned to undetectable levels by day 28. In susceptible mice, class I MHC expression in the CNS persisted and was intense in the white matter of the spinal cord throughout chronic infection and demyelination. No class I MHC expression was detected in the CNS of uninfected mice. Coexpression of viral RNA and class I MHC antigen was demonstrated in CNS cells by using simultaneous in situ hybridization and immunoperoxidase technique. These results support the hypothesis that a class I-restricted immune response directed against virus-infected cells may be important in the mechanism of demyelination.
 ...
PMID:Coexpression of class I major histocompatibility antigen and viral RNA in central nervous system of mice infected with Theiler's virus: a model for multiple sclerosis. 143 36

Myelin/oligodendrocyte glycoprotein (MOG) is a primary target autoantigen in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis. We have isolated several rat MOG cDNAs and confirmed their identity by comparison with MOG N-terminal peptide sequence. As expected, MOG mRNA expression is CNS-specific and peaks during active myelination. Our studies show that full length MOG mRNA is approximately 1.6 kb and encodes a signal peptide of 27 amino acids, followed by 218 residues for mature MOG (24,962 MW). A single site for N-glycosylation is found at Asn-31. Rather than the ubiquitous AAUAAA polyadenylation signal, a series of three overlapping, rare poly A signals were identified. The N-terminal half of mature MOG shares 52% identity with bovine butyrophilin, a possible lipid receptor. This same region has 39% identity with chicken B-G antigen, a major histocompatibility complex antigen involved in B cell selection and immune repertoire development. We show that both MOG and butyrophilin, each exhibiting a single Ig-like variable region domain, meet criteria for inclusion in the immunoglobulin superfamily. Moreover, MOG appears to represent a unique member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane-spanning domain or glycophospholipid anchor found in all other members of Ig superfamily members.
 ...
PMID:Myelin/oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily. 145 82

A body of literature exists implicating the major histocompatibility complex class II E molecule in development of immune tolerance and/or immunosuppression. To define better the regulatory mechanisms underlying susceptibility to experimental autoimmune encephalomyelitis, an autoimmune condition displaying major histocompatibility complex-II dependence, disease was induced in transgenic mice expressing a major histocompatibility complex-II E alpha d-transgene. This was compared with experimental autoimmune encephalomyelitis induced in age-matched E-negative, non-transgenic mice of the same strain. The results showed that experimental autoimmune encephalomyelitis could be induced by adoptive transfer methodology in both transgenic and non-transgenic mice of the A.CA (H-2f) strain. Virtually no differences were observed between the two mouse types with regard to disease onset, course, and neuropathology. The main difference noted was within nonirradiated recipient subgroups where the nonirradiated transgenic A.CA mice demonstrated greater inflammation and demyelination than the nonirradiated, non-transgenic mice throughout the disease course. Thus, the results did not support the idea that the E molecule, per se, is involved in the induction of tolerance or immunosuppressive mechanisms protecting against autoimmunity. In addition, histologic changes in the central nervous system of the A.CA strain, both transgenic and non-transgenic, differed in several respects from the changes observed in other more commonly studied susceptible strains. In A.CA mice, polymorphonuclear cells were a more prominent component of the acute inflammatory infiltrate and in chronic disease, large aggregates of lipid-laden macrophages and cholesterol clefts were present within white matter lesions. The present approach, using genetic manipulation of the immune system, may have relevance to the study of disease mechanisms in other putative autoimmune demyelinating disorders such as multiple sclerosis.
 ...
PMID:Autoimmune demyelination in transgenic E alpha d-positive A.CA mice. Comparison with E-negative A.CA mice. 157 54

Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which induces a chronic demyelinating disease of the central nervous system (CNS) in certain susceptible mouse strains. Demyelination has been shown to result from immunopathological responses mediated by CD4+, major histocompatibility complex (MHC) class II-restricted T cells. As little or no class II is expressed in the normal mouse CNS, the ability of astrocytes to express these proteins and present antigen to T cells from TMEV-infected mice was investigated here. It is shown that astrocytes are capable of presenting TMEV to virus-specific T cells in vitro, and that this ability is dependent on prior induction of MHC class II by interferon-gamma (IFN-gamma) treatment. Unlike other viruses such as murine hepatitis virus-JHM (a coronavirus) and measles, TMEV is not capable of inducing class II on astrocytes directly. There is a correlation between the ease of class II induction on astrocytes from different mouse strains by IFN-gamma and mouse strain susceptibility to TMEV-induced demyelinating disease. These results suggest that following viral infection and initial T-cell infiltration into the CNS, class II induction on astrocytes is a key step allowing local antigen presentation and amplification of immunopathological responses within the CNS and hence the development of demyelinating disease.
 ...
PMID:Susceptibility to Theiler's virus-induced demyelinating disease correlates with astrocyte class II induction and antigen presentation. 162 91


1 2 3 4 5 6 7 8 9 10 Next >>