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)

During a spontaneous outbreak of Theiler's encephalomyelitis severe combined immunodeficient mice developed high morbidity and high mortality. Histological lesions were localized in the ventral horns of the spinal cord and brain stem. The salient features were the severe vacuolar degeneration of neurones and glial cells and the absence of inflammatory cellular infiltrates. The clinical and pathological features of this outbreak indicate that the SCID mouse would be a much improved model for studying the mechanism of poliovirus infection and of virus-induced demyelinating diseases.
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PMID:Vacuolar neuronal degeneration in the ventral horns of SCID mice in naturally occurring Theiler's encephalomyelitis. 129 87

Humoral immunity is important for protection against viral infection and neutralization of extracellular virus, but clearance of virus from infected tissues is thought to be mediated solely by cellular immunity. However, in a SCID mouse model of persistent alphavirus encephalomyelitis, adoptive transfer of hyperimmune serum resulted in clearance of infectious virus and viral RNA from the nervous system, whereas adoptive transfer of sensitized T lymphocytes had no effect on viral replication. Three monoclonal antibodies to two different epitopes on the E2 envelope glycoprotein mediated viral clearance. Treatment of alphavirus-infected primary cultured rat neurons with these monoclonal antibodies to E2 resulted in decreased viral protein synthesis, followed by gradual termination of mature infectious virion production. Thus, antibody can mediate clearance of alphavirus infection from neurons by restricting viral gene expression.
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PMID:Antibody-mediated clearance of alphavirus infection from neurons. 165 36

We investigated whether myelin basic protein (MBP)-reactive T cells from multiple sclerosis (MS) patients can recognize mouse MBP since this is an expected requirement for the transfer of experimental autoimmune encephalomyelitis (EAE) into severe combined immunodeficiency (SCID) mouse-human chimeras. Peripheral blood mononuclear cells from 11 MS patients were analyzed for in vitro proliferation to mouse MBP. Six patients (55%) responded to mouse MBP at the first or second stimulation. Five T cell lines, selected with mouse MBP from five MS patients, were analyzed for their proliferation to mouse and human MBP and to a panel of synthetic peptides of human MBP. Four of the five lines recognized mouse MBP. In vitro proliferation was restricted by MHC class II in one line tested for MHC restriction. One of the five lines recognized whole human MBP and all five of the lines responded to at least one of the five synthetic peptides corresponding to human MBP residues 8-28, 67-90, 84-102, 87-99 or 130-149. These results show that MS patient T cells recognize mouse MBP and suggest that distinct human MBP epitopes are immunologically cross-reactive with epitopes of mouse MBP.
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PMID:Human myelin basic protein (MBP) epitopes recognized by mouse MBP-selected T cell lines from multiple sclerosis patients. 750 96

Cells of the central nervous system (CNS) normally do not express detectable levels of major histocompatibility complex (MHC) Class I antigens. However, MHC Class I expression can be induced after virus infection. We tested the hypothesis that virus-induced Class I expression is mediated by lymphocytes or cytokines using lymphocyte- and cytokine-deficient mice. We used Theiler's murine encephalomyelitis virus (TMEV), which induces CNS demyelination that maps genetically to the D region of MHC Class I and is associated with high levels of Class I products. TMEV infection of severe combined immunodeficiency (SCID) and recombination activation gene-1-deficient mice, which lack B and T lymphocytes, resulted in equivalent H-2D and H-2K expression in brain and spinal cord, according to analysis of the area and intensity of immunoperoxidase staining. Class I antigens were demonstrated as early as 6 hours after infection, and they were more widely distributed than viral RNA, indicating that expression was induced indirectly via a soluble factor. To determine whether cytokines induced the expression, we infected mice lacking receptors for interferon-alpha/beta (IFN-alpha/beta R (-/-)), interferon-gamma (IFN-gamma R(-/-)), and tumor necrosis factor-alpha (TNFRp55(-/-)). TMEV-infected IFN-gamma R(-/-) and TN-FRp55(-/-) mice expressed Class I antigens in the CNS, whereas IFN-alpha/beta R(-/-) mice did not, establishing that IFN-alpha/beta mediated the expression. In contrast to the equivalent expression in SCID mice, we observed greater area and higher intensity of H-2D versus H-2K antigens in infected SCID mice reconstituted with normal spleen cells. Collectively, the data indicate that after TMEV infection, early generalized MHC Class I expression is mediated by IFN-alpha/beta independently of lymphocytes, but the differential regulation of H-2D over H-2K may be controlled by B and/or T lymphocytes.
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PMID:Interferon alpha/beta mediates early virus-induced expression of H-2D and H-2K in the central nervous system. 925 80

Since Morton and Siegel's epochal experiments 30 years ago animal models have been successfully utilized both for transfer and resolution of autoimmune diseases (AID). More recently human lymphocyte xenografts have reproduced clinical AID in SCID mice. Allogeneic stem cell transplantation demonstrated therapeutic potential in fully developed autoimmune disease. Mixed allogeneic chimerism induced by a sublethal approach has also been shown to prevent and even reverse autoimmune insulitis in nonobese diabetic (NOD) mice. More unexpectedly it was found that experimental adjuvant arthritis (AA) and experimental allergic encephalomyelitis (EAE) could be cured by means of total body irradiation (TBI) followed by autologous hemolymphopoietic stem cell (HSC) transplantation. It was postulated that the newly developing T cells might be tolerant to self antigens. The transfer of AID from affected donors to recipients of allogeneic HSC transplants has been reported for many organ-specific AID, including diabetes (IDDM), thyroiditis, myasthenia gravis and thrombocytopenic purpura (AITP); rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were not transferred. Conversely patients with the combination of AID and a severe blood disease (leukemia, aplasia) were cured of both diseases following allogeneic BMT, with the notable exception of a relapse in a patient with RA despite full donor engraftment. Allogeneic transplants are certainly more promising as far as concerns a resolution of AID, because they may also exert a graft-versus-autoimmunity effect by gradually eradicating the recipient's lymphopoiesis, but transplant related mortality (TRM) is considered still too high to employ this procedure consistently. New non-myeloablative conditioning regimens, designed to allow the donor's immune system to take over, are already utilized for malignant and non-malignant hematologic diseases, and may become an attractive option for severe, refractory AID. For the time being, however, autologous procedures are still safer, and are being utilized in many projects worldwide. The EBMT/EULAR Registry has collected over 70 patient reports. The more numerous and favorable results have been obtained up to now in multiple scleosis and in systemic lupus erythematosus; the worst in refractory autoimmune thrombocytopenic purpura. No definite conclusions as to the efficacy of autologous HSC transplantation, from marrow or from blood, with or without T-cell depletion, may be drawn at this time, but the feeling is that real cures will be very difficult to obtain by this approach, and that corticosteroid-free remissions and a general lowering of the autoimmune potential will be more realistic goals. Accurate comparisons with already existing aggressive immunosuppressive protocols will become necessary, if possible by means of prospective randomized clinical studies.
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PMID:Stem cell transplantation for severe autoimmune diseases: progress and problems. 979 58

Myelin basic protein (BP)-specific T lymphocyte cell lines were selected from the lymph nodes (LN) of BP-immunized, H-2d, CXJ-1 mice prior to the onset of clinical disease. These CD4+ T cells induced severe acute experimental autoimmune encephalomyelitis (EAE) in MHC-compatible (H-2d), lymphocyte-deficient (SCID) mice (C.B-17scid/scid). The incidence of disease was much higher in immunodeficient SCID mice (71%) than in syngeneic immunocompetent CXJ-1 mice (5%). SCID mice with EAE had an acute progressive paralytic disease with inflammation and myelin loss detected in the spinal cord. Eighty-six percent (12/14) of mice followed for more than 2 weeks had 1 or more relapses of EAE. These results demonstrate that clinical remission and relapse of EAE can be induced by the single adoptive transfer of a LN-derived BP-specific T cell line in the absence of host-derived effector and regulatory lymphocytes. Furthermore, the data demonstrate that the pathogenic potential of BP-specific T cells is greater in lymphocyte-deficient SCID mice compared with immunocompetent mice, suggesting that autoreactive T cells are controlled by potent inhibitory mechanisms associated with regulatory lymphocytes. These results are relevant to mechanisms of disease remission and relapse mediated by lymphocytes involved in paralytic inflammatory diseases such as multiple sclerosis (MS).
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PMID:Myelin basic protein-specific T lymphocytes induce chronic relapsing experimental autoimmune encephalomyelitis in lymphocyte-deficient (SCID) mice. 1037 72

Given the critical role of cytokines in the regulation of an inflammatory response, we investigated whether certain cytokines are expressed in the brains of normal mice during maturation that could contribute to the immune-privileged nature of the CNS or potentially influence an immune-mediated illness such as experimental allergic encephalomyelitis. The gene expression of IFN gamma (Th1 cytokine) and IL-4 (Th2 cytokine) was analyzed in the brain of several strains of mice. IFN gamma was not detectable. However, IL-4 was present in the brains of neonatal mice, but not adult mice. Resident CNS cells are believed to be the source of the IL-4, because mice deficient in T cells (SCID and RAG2-/-) expressed the IL-4 gene in the CNS. Further analysis indicated that the gene expression of the Th2 cytokine transcription factor, GATA-3, correlated with IL-4 and IL-10 expression in the brain. Since GATA-3-deficient mice have an abnormal CNS, brain-derived Th2 cytokines may play an important role in CNS development, as well as potentially contribute to the immune-privileged nature of the brain.
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PMID:Developmentally regulated gene expression of Th2 cytokines in the brain. 1086 98

Certain cells within the CNS, microglial cells and perivascular macrophages, develop from hemopoietic myelomonocytic lineage progenitors in the bone marrow (BM). Such BM-derived cells function as CNS APC during the development of T cell-mediated paralytic inflammation in diseases such as experimental autoimmune encephalomyelitis and multiple sclerosis. We used a novel, interspecies, rat-into-mouse T cell and/or BM cell-transfer method to examine the development and function of BM-derived APC in the CNS. Activated rat T cells, specific for either myelin or nonmyelin Ag, entered the SCID mouse CNS within 3-5 days of cell transfer and caused an accelerated recruitment of BM-derived APC into the CNS. Rat APC in the mouse CNS developed from transferred rat BM within an 8-day period and were entirely sufficient for induction of CNS inflammation and paralysis mediated by myelin-specific rat T cells. The results demonstrate that T cells modulate the development of BM-derived CNS APC in an Ag-independent fashion. This previously unrecognized regulatory pathway, governing the presence of functional APC in the CNS, may be relevant to pathogenesis in experimental autoimmune encephalomyelitis, multiple sclerosis, and/or other CNS diseases involving myelomonocytic lineage cells.
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PMID:T lymphocytes promote the development of bone marrow-derived APC in the central nervous system. 1112 14

The sequential emergence of specific T lymphocyte-mediated immune reactivity directed against multiple distinct myelin epitopes (epitope spreading) has been associated with clinical relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Based on this association, an appealing and plausible model for immune-mediated progression of the advancing clinical course in MS and EAE has been proposed in which epitope spreading is the cause of clinical relapses in T cell-mediated CNS inflammatory diseases. However, the observed association between epitope spreading and disease progression is not universal, and absolute requirements for epitope spreading in progressive EAE have not been tested in the absence of multiple T cell specificities, because most prior studies have been conducted in immunocompetent mouse strains that possessed broad TCR repertoires. Consequently, the precise nature of a causal relationship between epitope spreading and disease progression remains uncertain. To determine whether relapsing or progressive EAE can occur in the absence of epitope spreading, we evaluated the course of disease in mice which possessed only a single myelin-specific TCR. These mice (transgenic/SCID +/+) exhibited a progressive and sometimes remitting/relapsing disease course in the absence of immune reactivity to multiple, spreading myelin epitopes. The results provide direct experimental evidence relevant to discussions on the mechanisms of disease progression in MS and EAE.
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PMID:Epitope spreading is not required for relapses in experimental autoimmune encephalomyelitis. 1257 32

Expression of the CD45 Ag in hemopoietic cells is essential for normal development and function of lymphocytes, and both mice and humans lacking expression exhibit SCID. Human genetic variants of CD45, the exon 4 C77G and exon 6 A138G alleles, which alter the pattern of CD45 isoform expression, are associated with autoimmune and infectious diseases. We constructed transgenic mice expressing either an altered level or combination of CD45 isoforms. We show that the total level of CD45 expressed is crucial for normal TCR signaling, lymphocyte proliferation, and cytokine production. Most importantly, transgenic lines with a normal level, but altered combinations of CD45 isoforms, CD45(RABC/+) and CD45(RO/+) mice, which mimic variant CD45 expression in C77G and A138G humans, show more rapid onset and increased severity of experimental autoimmune encephalomyelitis. CD45(RO/+) cells produce more TNF-alpha and IFN-gamma. Thus, for the first time, we have shown experimentally that it is the combination of CD45 isoforms that affects immune function and disease.
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PMID:Combinations of CD45 isoforms are crucial for immune function and disease. 1651 10


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