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)

Research into the pathogenesis of multiple sclerosis (MS) has focused on myelin antigens as potential targets of autoimmune attack. Proteolipid protein (PLP), which makes up more than 50% of central nervous system myelin, is a hydrophobic membrane protein with many properties that historically have made it difficult to study. The use of synthetic peptides based on the PLP sequence provides an alternative method for studying the immunological properties of PLP. Using peripheral blood lymphocytes from MS patients, long-term TCL established in the presence of PLP reacted weakly to PLP in proliferation assays; however, these same lines were much more reactive to synthetic peptides of PLP. Thus, we established short-term T cell lines (TCL) from the peripheral blood lymphocytes (PBL) of MS patients in the presence of five separate synthetic PLP peptides. In six out of seven MS patients, proliferative responses were elicited most often to PLP 40-60 compared to four other PLP peptides (PLP 89-106, 103-120, 125-143, and 139-154). Characterization of PLP 40-60-responsive TCL from a single MS patient, MS1, indicated that six out of seven TCL proliferating to the peptide also lysed PLP 40-60 pulsed autologous targets. All cytolytic PLP 40-60 TCL were CD4+ and MHC class II restricted and further analysis of MS1 TCL showed that the PLP 40-60 TCL were restricted by DR4 whereas the MBP TCL from MS1 were restricted by DR6. These findings suggest that difficulties in examining the immune response to PLP have been due to the poor response generated in vitro using the whole molecule and that the use of synthetic peptides may represent an alternative approach to the study of PLP. These results also suggest that MS PBL recognize several PLP peptides, with the predominant response to PLP 40-60. Since these cells phenotypically resemble T cells known to mediate experimental autoimmune encephalomyelitis, it is possible that they may play a role in the pathogenesis of MS.
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PMID:Identification of a novel T cell epitope of human proteolipid protein (residues 40-60) recognized by proliferative and cytolytic CD4+ T cells from multiple sclerosis patients. 768 93

About 50% of the mononuclear cells in the perivascular lesions in the central nervous system (CNS) of rats suffering from experimental allergic encephalomyelitis (EAE) are blood-borne macrophages. In this study we investigated the role of these macrophages in different variants of EAE, using a liposome-mediated macrophage depletion technique. Intravenously injected liposomes containing dichloromethylene diphosphonate (Cl2MDP) are ingested by macrophages and cause temporary and selective elimination of these cells. Macrophage depletion during EAE induced by a T cell line specific for myelin basic protein (MBP; T cell-EAE) suppresses development of neurological signs of EAE. T cell-EAE with pronounced demyelination as induced by an additionally injected MoAb directed against myelin oligodendrocyte glycoprotein (MOG) was also significantly ameliorated after macrophage depletion. During chronic relapsing EAE (CR-EAE) the occurrence of relapses was prevented or suppressed, provided that the liposomes were injected before the initiation of a putative relapse. A chronic progressive course of CR-EAE was not modified by Cl2MDP containing liposome treatment. Histologic examination of the CNS of liposome-treated animals confirmed decreased infiltration of macrophages into the parenchyma in the rats with T cell and AD-EAE, whereas T cells were still present.
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PMID:Macrophages in T cell line-mediated, demyelinating, and chronic relapsing experimental autoimmune encephalomyelitis in Lewis rats. 774 75

gamma delta T cells are over-represented in some multiple sclerosis (MS) parenchymal lesions and in the cerebrospinal fluid (CSF) of individuals with early MS. In this investigation we studied the T cell-T cell interactions between human, myelin basic protein-reactive T cells and peripheral blood mononuclear cells (PBMC) isolated from MS and control subjects. We detected brisk proliferation by PBMC in response to activated, but not resting, MBP-specific T cells. The magnitude of proliferation approached that induced by superantigens and was distinctly greater than the response to standard recall antigens. Examination of the responding T cells revealed predominant expansion of T cells using gamma delta rather than alpha beta T cell receptors. This finding suggests that the accumulation of gamma delta T cells noted in some MS parenchymal lesions may represent recruitment by activation markers expressed by other T cells in these lesions. The response to activated but not resting MBP-specific T cells may parallel observations that protective T cell vaccination in experimental encephalomyelitis is more effective using activated rather than resting, myelin-specific T cells.
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PMID:Gamma delta T cells participate in the immune response against activated, myelin basic protein-specific, human T cells. 775 6

Nuclear magnetic resonance imaging (MRI) proved to be, from the first, a very sensitive method, allowing the visualisation of multiple sclerosis lesions, yet which never permitted to establish a non equivocal relationship between the semeiology of such lesions and the clinical signs. The multifocal aspect of disseminated multiple sclerosis lesions is probably one of several factors accounting for this discrepancy. The study of an autoimmune disease, experimental allergic encephalomyelitis (EAE), regarded as a suitable model for multiple sclerosis in humans, has been performed using MRI in order to unravel the pathogenesis of the disease and apprehend the mechanisms responsible for the formation of multiple sclerosis lesions. The study focused on the part played by the blood-brain barrier (BBB) in the induction process of an autoimmune disease, since the central nervous system is normally screened from immunological supervision, by this barrier. Models both of acute EAE, induced by active or passive transfer of the antigen (myelin basic protein-MBP)--and chronic EAE, induced by passive transfer of MBP-specific T cells and myelin glycoproteins or MOG-specific monoclonal antibodies, have been reproduced, and their evolution followed up using high field MRI. Every time, the crucial role of the BBB was evidenced by the synchronism existing between the clinical signs, the appearance of lesions, preferentially in the most sensitive or permeable areas, and the BBB breakdown encouraged by the action of adjuvants. The physiopathological study of EAE using MRI is suggestive of the concept of systemic disease for multiple sclerosis, according to a two-step process, involving, in a first stage some primary viral or bacterial infection, causing T-cells to be sensitized to the host's own proteins by molecular mimicry, and in a second stage some bacterial infection or accidental circumstances which, resulting in a BBB breakdown, would provide immunocompetent cells with an opportunity to reach their target.
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PMID:[Magnetic Resonance Imaging study of the role of the blood-brain barrier in the pathogenesis of experimental allergic encephalomyelitis: application to multiple sclerosis]. 778 36

Expression of adhesion molecules in immune-mediated diseases of the central nervous system was reviewed. In multiple sclerosis and experimental allergic encephalomyelitis (EAE), endothelial cells of active lesions increase expression of the adhesion molecules such as ICAM-1, VCAM-1 and inflammatory cells including memory T cells and macrophages express high levels of adhesion molecules such as LFA-1, VLA-4. Astrocytes also express CD44, ICAM-1, VCAM-1 and E-selectin in response to cytokine stimuli. In EAE, the majority of infiltrating cells are not MBP-specific memory T cells, thus it is speculated that the up-regulation of the adhesion molecules in the endothelial cells plays a decisive role in the development of immune-mediated diseases of the central nervous system. Therapeutic potency of clinical usage of anti-adhesion molecule antibodies has been explored.
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PMID:[Adhesion molecules and immune-mediated diseases of the central nervous system]. 799 76

Resistance to experimental autoimmune encephalomyelitis (EAE) induced by vaccination with a peptide representing amino acids 39-59 of the rat T cell receptor (TCR) V beta 8 element has been ascribed to the induction of protective antibodies and T lymphocytes, both recognizing the V beta 8 TCR peptide (TCRP) as well as V beta 8 TCR-expressing encephalitogenic lymphocytes. In this study immunization with the V beta 8 TCR peptide conferred partial resistance to active induction of EAE in three of six rats. The immunoregulatory role of TCRP-specific T cells in resistance to EAE was investigated. In vitro, CD4+ T cell lines reactive with the V beta 8 TCRP did not respond to encephalitogenic V beta 8 TCR-bearing cell lines nor did they impair their MBP-induced activation. In vivo, activated TCRP-specific line cells did not ameliorate actively induced EAE. The beneficial effect of V beta 8 TCRP-vaccination on the course of EAE may be due to the induction of protective antibodies. Neither before, nor during or after EAE did we observe a cellular response to the V beta 8 TCRP in lymph nodes or spleens of MBP-immunized animals. Moreover, we were not able to establish TCRP-specific T cell lines from EAE rats, but from all rats immunized with the TCRP. Our data do not support the assumption that V beta 8 TCRP-reactive CD4+ T cells are the population operative in resistance to EAE after recovery from disease.
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PMID:Modulation of EAE by vaccination with T cell receptor peptides: V beta 8 T cell receptor peptide-specific CD4+ lymphocytes lack direct immunoregulatory activity. 790 10

The development of autoimmune disease is accompanied by the acquired recognition of new self-determinants, a process commonly referred to as determinant spreading. In this study, we addressed the question of whether determinant spreading is pathogenic for progression of chronic-relapsing experimental autoimmune encephalomyelitis (EAE), a disease with many similarities to multiple sclerosis (MS). Our approach involved a systematic epitope mapping of responses to myelin proteolipid protein (PLP) as well as assaying responses to known encephalitogenic determinants of myelin basic protein (MBP 87-89) and myelin oligodendrocyte glycoprotein (MOG 92-106) at various times after induction of EAE in (SWR X SJL)F1 mice immunized with PLP 139-151. We found that the order in which new determinants are recognized during the course of disease follows a predictable sequential pattern. At monthly intervals after immunization with p139-151, responses to PLP 249-273, MBP 87-99, and PLP 137-198 were sequentially accumulated in al mice examined. Three lines of evidence showed that determinant spreading is pathogenic for disease progression: (a) spreading determinants mediate passive transfer of acute EAE in naive (SWR X SJL)F1 recipients; (b) an invariant relationship exists between the development of relapse/progression and the spreading of recognition to new immunodominant encephalitogenic determinants; and (c) after EAE onset, the induction of peptide-specific tolerance to spreading but not to nonspreading encephalitogenic determinants prevents subsequent progression of EAE. Thus, the predictability of acquired self-determinant recognition provides a basis for sequential determinant-specific therapeutic intervention after onset of the autoimmune disease process.
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PMID:A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: a basis for peptide-specific therapy after onset of clinical disease. 866 34

Activation of the vascular endothelium is important in the development of inflammation. Activated endothelial cells (EC) express surface markers not expressed by quiescent EC. These surface markers augment adhesion reactions and leukocyte migration. We examined microvessel EC activation longitudinally in experimental autoimmune encephalomyelitis (EAE) in Lewis rats. CNS microvessels were isolated at 0, 3, 7, 12, 20, and 30 days post-inoculation (PI). Normal and CFA-injected rat microvessels do not express activation antigens (Ag). Increased expression of major histocompatibility complex (MHC) class II molecule and intercellular adhesion molecule-1 (ICAM-1) were detected on CNS microvessels from immunized rats at 7 days PI, prior to development of clinical signs, and at 12 days PI. Enhanced MHC class I molecule was seen only at 12 days. MHC class II molecule expression was focally expressed along microvessel fragments. By 20 days PI, EC did not exhibit increased levels of any of the markers tested. Perivascular cells (possibly pericytes), however, were found to express MHC class II molecule and ICAM-1 up to 30 days PI. During the recovery phase isolated CNS microvessels from MBP-immunized rats were unresponsive to IFN gamma-mediated endothelial activation. Unresponsiveness was independent of IFN gamma concentration. These results suggest that the endothelium is restored to functional quiescence during the recovery phase of acute EAE.
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PMID:Recovery phase of acute experimental autoimmune encephalomyelitis in rats corresponds to development of endothelial cell unresponsiveness to interferon gamma activation. 872 61

Chronic progression of autoimmune disease is accompanied by the acquisition of autoreactivity to new self-determinants. Recent evidence indicates that this process, commonly referred to as determinant spreading, may be pathogenic for chronicity. Our studies on experimental autoimmune encephalomyelitis (EAE), a murine model widely used in multiple sclerosis (MS) studies, have shown that determinant spreading develops as a predictable sequential cascade of neo-autoimmunity during progression to chronic disease. By 7-8 weeks after immunization of (SWR x SJL)F1 mice with the immunodominant myelin proteolipid protein determinant (PLP 139-151), splenocytes consistently respond to the immunodominant myelin basic protein determinant (MBP 87-99). In the present study, we directly address the pathogenicity of neo-autoimmunity resulting from endogenous self-priming during the course of disease. Our results indicate that T cells responding to the spreading MBP 87-99 determinant produce a proinflammatory cytokine profile consistent with type 1 helper T cells (Th1) cells. In addition, splenocytes activated to the spreading MBP 87-99 determinant consistently transfer acute EAE in naive recipients even when T cells reactive to the priming PLP 139-151 immunogen are eliminated by bromodeoxyuridine (BUdR)-mediated photolysis. Our data indicate that endogenous neo-autoantigen priming during chronic autoimmune disease generates type 1 helper T cells (Th1) cells that are autonomously pathogenic. These results provide further evidence supporting the view that determinant spreading is a pathogenic process that leads to chronic progression of autoimmune disease.
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PMID:Generation of autonomously pathogenic neo-autoreactive Th1 cells during the development of the determinant spreading cascade in murine autoimmune encephalomyelitis. 887 7

Previous studies of experimental allergic encephalomyelitis (EAE) in the LER rat have suggested that amino acid differences present in the LER TCR V beta 8.2 chain may be associated with disease resistance. We report here that LEW rats bred to express a V beta 8.2 gene from DA rats, identical to that found in LER, are susceptible to EAE induction. Furthermore, T cells infiltrating the spinal cord of diseased animals primarily utilized V beta 8.2 and the associated AspSer CDR3 motif, typical of TCR V beta 8.2 chains expressed by pathogenic, anti-MBP responsive T cells in the LEW rat.
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PMID:Analysis of T cell receptor beta chains in the rat: I. Allelic polymorphism of V beta 8.2 is not a predisposing genetic factor in susceptibility to experimental allergic encephalomyelitis. 889 81


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