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)

We characterized the effector cells which mediate experimental autoimmune encephalomyelitis (EAE) on the basis of selective adherence properties. Nylon-nonadherent spleen cells (SpC) from Lewis rats challenged earlier with myelin basic protein (BP) in adjuvant were separated by 'panning' on Petri dishes coated with monoclonal antibody (MAb) OX22. OX22 recognizes high molecular weight forms of the leukocyte-common antigen which is present on several cell types, including the CD4-positive T cells which mediate delayed hypersensitivity reactions. We found that the EAE effector cells were enriched in the OX22-adherent T cell population, which supports the hypothesis that delayed hypersensitivity is important in the pathogenesis of this autoimmune disease.
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PMID:Effector cells of autoimmune encephalomyelitis in the rat belong to the CD4-positive, OX22-adherent T cell subset. 258 91

The critical role of tumor necrosis factor (TNF) as a mediator in autoimmune inflammatory processes is evident from in vivo studies with TNF-blocking agents. However, the mechanisms by which TNF, and possibly also its homologue lymphotoxin alpha, contributes to development of pathology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear. Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage. Here we show that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical signs of actively induced experimental autoimmune encephalomyelitis. Significantly, the total number of CD4+ T lymphocytes isolated from the central nervous system of clinically healthy treated versus diseased control animals was comparable. By using a CD45 congenic model of passively transferred experimental autoimmune encephalomyelitis to enable tracking of myelin basic protein-specific effector T lymphocytes, prevention of clinical signs of disease was again demonstrated in treated animals but without quantitative or qualitative impediment to the movement of autoreactive T lymphocytes to and within the central nervous system. Thus, despite the uninterrupted movement of specific T lymphocytes into the target tissue, subsequent disease development was blocked. This provides compelling evidence for a direct effector role of TNF/lymphotoxin alpha in autoimmune tissue damage.
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PMID:Unimpaired autoreactive T-cell traffic within the central nervous system during tumor necrosis factor receptor-mediated inhibition of experimental autoimmune encephalomyelitis. 747 38

Ramified microglia in the adult central nervous system (CNS) are the principal glial element up-regulating MHC class I and II expression in response to inflammatory events or neuronal damage. A proportion of these cells also express MHC class II constitutively in the normal CNS. The role of microglia as APCs for CD4+ T cells extravasating into the CNS remains undefined. In this study, using irradiation bone marrow chimeras in CD45-congenic rats, the phenotype CD45lowCD11b/c+ is shown to identify microglial cells specifically within the CNS. Highly purified populations of microglia and nonmicroglial but CNS-associated macrophages (CD45highCD11b/c+) have been obtained directly from the adult CNS, by using flow cytometric sorting. Morphologically, freshly isolated microglia vs other CNS macrophages are quite distinct. Of the two populations recovered from the normal CNS, it is the minority CD45highCD11b/c+ transitional macrophage population, and not microglia, that is the effective APC for experimental autoimmune encephalomyelitis-inducing CD4+ myelin basic protein (MBP)-reactive T cells. CD45highCD11b/c+ CNS macrophages also stimulate MBP-reactive T cells without addition of MBP to culture, suggesting presentation of endogenous Ag. This is the first study in which microglia vs other CNS macrophages have been analyzed for APC ability directly from the CNS, with substantial cross-contamination between the two populations eliminated. The heterogeneity of these populations in terms of APC function is clearly demonstrated. Evidence is still lacking that adult CNS microglia have the capacity to interact with and stimulate CD4+ T cells to proliferate or secrete IL-2.
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PMID:Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. 772 89

The inflammatory cytokines IFN-gamma and TNF-alpha have been demonstrated in various autoimmune diseases, and are thought to participate in the induction and pathogenesis of disease. TFN-alpha is a cytopathic cytokine that is cytotoxic for oligodendrocytes in vitro and has been implicated in the pathology of multiple sclerosis and its animal model experimental allergic encephalomyelitis (EAE). We used reverse transcriptase (RT)-PCR to study the kinetics, cellular source, and regulation of cytokine gene expression in the central nervous system (CNS) of SJL/J mice with myelin basic protein-induced EAE at different stages of the disease. The expression of CD3, IL-2, IFN-gamma, and TNF-alpha mRNA was barely detectable in the CNS of unmanipulated mice or mice that were immunized with adjuvant but showed no symptoms. These mRNAs were readily detectable in the CNS of mice during peak disease, then coordinately dropped to background levels during remission. Analysis of cells isolated from the CNS of mice with acute EAE showed that the Th1 cytokines, IL-2 and IFN-gamma, were produced by infiltrating CD4+ T cells. In contrast, TNF-alpha was predominantly transcribed by non-T mononuclear CNS cells, the majority of which were identified as microglia and macrophages by their Mac-1 phenotype. Microglia could be discriminated by their low expression of CD45. Incubation of freshly derived, adult microglia from normal, uninfiltrated, CNS with activated Th1 supernatant induced the production of TNF-alpha mRNA. Therefore, TNF-alpha is made by both CNS-resident microglia and infiltrating macrophages during EAE, and this production is tightly controlled by cytokines secreted by infiltrating CD4+ T cells.
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PMID:TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by Th1 cytokines. 781 94

Inbred Buffalo rats (RT-1b) have been used in studies of experimental autoimmune encephalomyelitis and autoimmune thyroiditis. Since our studies, and those of others, have relied on the genetic purity of inbred Buffalo rats, we chose to test these animals for expression of strain-dependent, allotype-specific variants of CD45 (leukocyte common antigen, LCA) using the monoclonal antibodies RT7.1 and RT7.2. The goal of this study was to confirm the genetic purity and to verify the inbred status of Buffalo rats obtained from a commercial source.
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PMID:Evidence for genetic contamination of inbred buffalo rats (RT-1b) obtained from a commercial vendor. 803 60

Cytokines are important mediators in the pathogenesis of central nervous system (CNS) inflammatory diseases including multiple sclerosis (MS), experimental allergic encephalomyelitis (EAE), viral encephalitis and virus induced demyelinating diseases. We have used immunohistochemical techniques to characterize the mononuclear cell infiltrate and cytokine profiles in the CNS following infection of mice with the demyelinating A7(74) strain of Semliki Forest virus (SFV), an important viral model of MS. Mononuclear cell infiltrates in the CNS, first observed at 3 days and maximal during clearance of infectious virus, were comprised predominantly of CD8+ lymphocytes. F4/80+ macrophage/microglia and CD45/B220+ B lymphocytes were most numerous during the subsequent phase of demyelination. CD4+ T-lymphocytes were observed at low levels throughout infection. By immunostaining MHC class I, IL-1beta , IL-3 and TGF beta1 were constitutively expressed in normal mice and were upregulated following infection. MHC class II, IL-1alpha, IL-2, IL-2R, TNF-alpha and IL-6 were strongly upregulated in the CNS of SFV-infected mice and mice with chronic relapsing EAE. The spatial and temporal distribution of these cytokines during the course of disease was analysed. Whereas IL-1alpha, IL-1beta, IL-10, and TGF beta1 were observed on day 3 following infection GMCSF, IL-2 and TNF alpha were first apparent at day 7 when the cellular infiltration in the CNS was most intense. In contrast IFN gamma and IL-6 were first observed on day 10 prior to the demyelination phase of disease. Cytokines in the lesions of demyelination suggest a role in the pathogeneisis of myelin damage. Based on cytokine profiles no clear bias of either a Th1 or Th2 response was observed in the CNS during infection.
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PMID:Characterization of the cellular and cytokine response in the central nervous system following Semliki Forest virus infection. 911 72

We have previously used antibodies to the NG2 proteoglycan and the alpha receptor for platelet-derived growth factor (PDGF alpha receptor) to identify oligodendroglial progenitor cells in vivo and in vitro. It has recently become evident that the GD3 antigen, which has been widely used as a marker for oligodendrocyte progenitor cells, is also expressed by microglial cells. In this study we have examined the relationship between the NG2+/PDGF alpha receptor+ glial progenitor cells and microglial cells in normal developing and mature rat brain and in inflammatory lesions in mice with experimental autoimmune encephalomyelitis (EAE). Double-labeling of sections from normal rat brain using anti-NG2 antibodies and lectin from Griffonia simplicifolia (GSA I-B4) or monoclonal antibody 4H1 indicated that there is no overlap between NG2+ glial progenitor cells and microglia in the parenchyma of the central nervous system. In EAE lesions, both NG2+ cells and microglia, identified by antibodies to F4/80 and CD45, displayed reactive changes characterized by increased cell number and staining intensity and shortening and thickening of cell processes. Both cell types were found surrounding perivascular infiltrates of lymphocytes. Double-labeling EAE sections for NG2 and F4/80 or CD45 failed to reveal cells that co-expressed both antigens, suggesting that reactive NG2+ cells are distinct from activated microglia. However, a close spatial relationship between NG2+ cells and microglia was observed in the normal brain and to a greater extent in EAE, where processes of an activated microglial cell were sometimes seen to encircle an NG2+ cell. These observations are indicative of a functional interaction between microglia and the NG2+ glial cells.
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PMID:Normal and reactive NG2+ glial cells are distinct from resting and activated microglia. 916 56

CD45 is involved in the regulation of lymphocyte activation, and it has been demonstrated that ligation of CD45 induces apoptosis of T and B lymphocytes. Recently anti-CD45RB antibody therapy was shown to block acute allograft rejection in a mouse model of transplantation. Therefore, we wanted to examine the effects of anti-CD45RB antibody treatment on the course of an autoimmune disorder, experimental allergic encephalomyelitis (EAE), a Th1-mediated process. Mice immunized with myelin basic protein and treated with anti-CD45RB antibody did not develop EAE. Histologically, there was no evidence of lymphocytic infiltrates in the central nervous system. T cell proliferation and TNF-alpha production were significantly decreased in anti-CD45RB-treated mice. Furthermore, there was a significant reduction in the production of other Th1 cytokines including interferon-gamma and IL-2, but not IL-4 or IL-6. However, levels of a number of adhesion markers or markers of activation such as VLA-4 and LFA-1 on T cells were no different in treated versus control animals. Thus, anti-CD45RB can prevent EAE and appears to do so by altering T cell proliferation and cytokine production.
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PMID:Prevention of experimental allergic encephalomyelitis by an antibody to CD45RB. 987 18

The mechanisms underlying the initiation of virus-induced autoimmune disease are not well understood. Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a mouse model of multiple sclerosis, is initiated by TMEV-specific CD4(+) T cells targeting virally infected central nervous system-resident (CNS-resident) antigen-presenting cells (APCs), leading to chronic activation of myelin epitope-specific CD4(+) T cells via epitope spreading. Here we show that F4/80(+), I-A(s+), CD45(+) macrophages/microglia isolated from the CNS of TMEV-infected SJL mice have the ability to endogenously process and present virus epitopes at both acute and chronic stages of the disease. Relevant to the initiation of virus-induced autoimmune disease, only CNS APCs isolated from TMEV-infected mice with preexisting myelin damage, not those isolated from naive mice or mice with acute disease, were able to endogenously present a variety of proteolipid protein epitopes to specific Th1 lines. These results offer a mechanism by which localized virus-induced, T cell-mediated inflammatory myelin destruction leads to the recruitment/activation of CNS-resident APCs that can process and present endogenous self epitopes to autoantigen-specific T cells, and thus provide a mechanistic basis by which epitope spreading occurs.
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PMID:Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler's virus-infected mice. 1048 65

Experimental allergic encephalomyelitis (EAE) was induced in the NIH minipig to create a large animal model of multiple sclerosis with a well-characterized immune system. Sixteen NIH minipigs were inoculated with minipig spinal cord homogenate (SCH). The clinical course was primarily monophasic, but re-induction was possible. CNS and blood lymphocytes specifically proliferated to SCH. Flow cytometry of CNS-isolated cells and SCH-stimulated PBMC revealed a shift to CD4(+) CD8(+) cells. Pathology demonstrated demyelination in the CNS white matter with perivascular mononuclear cell infiltrates of CD3(+)CD4(+)CD45(+) lymphocytes with a subset CD8(+). Pathology and in vitro SCH responses implicate a central role of CD4(+) lymphocytes in swine EAE.
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PMID:Induction of experimental allergic encephalomyelitis in the NIH minipig. 1071 59


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