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)

Experimental allergic encephalomyelitis has been shown to have an immunological basis. In fact, the disease can be induced by T cells specific for myelin basic protein, a molecule found in abundance in the central nervous system. In this article, Ellen Heber-Katz and Hans Acha-Orbea discuss the T-cell receptor (TCR) repertoire of the encephalitogenic T-cell response, and show that a limited V gene pool, in fact a single V beta and two V alpha families, are being used by the PL/J and B10.PL mice and by every rat strain examined, even though the antigenic determinants and the major histocompatibility complex (MHC) molecules are different in all cases. This extraordinary finding suggests that the TCR is involved in encephalitogenicity in a way that not only involves the recognition of antigen in association with MHC, but also as an effector molecule that results in encephalitis. If this is true, it implies that TCRs, in general, play more than one role in mammalian physiology.
 ...
PMID:The V-region disease hypothesis: evidence from autoimmune encephalomyelitis. 266 17

The oligodendrocyte (Od), a glial cell that produces myelin in the central nervous system, may be a target for autoreactive T cells in autoimmune demyelinating processes, although not expressing major histocompatibility complex (MHC) products. To analyze Od-T-cell interactions, we selected from normal SJL/J mouse splenocytes sensitized in vitro by Lewis rat Od a T-cell clone, named C2, exhibiting a surface phenotype of mature T cell (Thy 1+, CD3+, CD8+, CD4-, asialo-GM1-). C2 T cells displayed a specific cytotoxicity to syngeneic Od as well as to rat Od, but not to astrocytes or lymphoblasts, or to YAC-1 cells, a target for natural killer and lymphokine-activated killer activity. The T-cell receptor of clone C2 was found to be a CD3-associated alpha/beta-chain heterodimer similar to that usually expressed by antigen-specific MHC-restricted mature T cells. Attempts to block the C2-mediated cytolysis by a series of monoclonal antibodies showed that both the CD3-T-cell receptor complex and the CD8 accessory molecule were required for OD-T-cell interaction and confirmed the lack of involvement of polymorphic MHC products as epitope-presenting structures. Antibodies directed against a surface Od glycoprotein, previously shown to elicit demyelinating autoantibodies in experimental autoimmune encephalomyelitis, fully blocked the cytotoxicity of T-cell clone C2 to its Od target. These data suggest that an epitope of a surface Od glycoprotein may be directly and specifically recognized and killed by autoreactive T cells expressing an alpha/beta receptor without conventional MHC restriction.
 ...
PMID:Oligodendrocyte-specific autoreactive T cells using an alpha/beta T-cell receptor kill their target without self restriction. 278 60

The effect of unilateral peripheral nerve lesions on the inflammatory response of experimental allergic encephalomyelitis (EAE) in rat central nervous system (CNS) was studied. Immunostaining for major histocompatibility complex (MHC) antigens and T-cell subsets demonstrated that MHC class I expression was markedly enhanced in as well as around axotomized motor neurons and that MHC class II expression was induced on several cells, probably microglial cells, in close proximity to the axotomized motor neurons. There was also a pronounced increase in interleukin 2 receptor-positive lymphocytes as well as T-cells and the T-cell subsets on the injured as compared to the non-injured contralateral side. These effects were present particularly in the initial phase of EAE and persisted for several weeks. The results suggest that neurons may communicate immunoregulatory signals to their microenvironment and that retrograde axonal signals from the distant periphery may alter the immune response locally within the CNS.
 ...
PMID:Local enhancement of major histocompatibility complex (MHC) class I and II expression and cell infiltration in experimental allergic encephalomyelitis around axotomized motor neurons. 278 5

Theiler's murine encephalomyelitis virus (TMEV) causes immune-mediated demyelination in susceptible mice which is similar to human demyelinating disorders such as multiple sclerosis. In addition, the picornavirus persists within the central nervous system throughout the course of the chronic demyelinating disease. This article reviews the neuropathology, virology, immunology, and molecular biology of the model system. We analyze the possible mechanisms by which this virus induces demyelination and persists in the nervous system. Finally, we provide a hypothesis that the specificity of primary white matter destruction in the TMEV model depends on immune-sensitized cells which interact with viral antigen plus major histocompatibility complex (MHC) antigens on the surfaces of oligodendrocytes or myelin sheaths.
 ...
PMID:Theiler's murine encephalomyelitis: a model of demyelination and persistence of virus. 282 57

Cell-mediated immune mechanisms contribute to tissue injury within the central nervous system (CNS) in a number of experimental diseases, including experimental allergic encephalomyelitis and some viral infections, and may mediate lesion formation in multiple sclerosis. We investigated the conditions under which murine astrocytes can become susceptible targets of cytotoxic T cells. We demonstrate that mouse astrocytes in vitro can be susceptible targets of class I major histocompatibility complex (MHC)-specific cytotoxicity mediated by L3 cytotoxic T lymphocytes (CTL). Expression of appropriate class I MHC antigen on the astrocytes is a requirement, because only cells bearing the H-2d phenotype are susceptible to lysis by L3 cells. BALB/c-H-2dm2 astrocytes lacking the specific determinant recognized by L3 cells are not susceptible to lysis. Astrocyte lysis can, however, occur under culture conditions in which MHC antigen expression is immunocytochemically low or undetectable. Cytolysis can be inhibited by pretreatment of the effector L3 cells with either anti-Lyt-2 monoclonal antibody (mAb) or anti-clonotypic mAb and by preincubation of the glial target cells with an appropriate anti-H-2 antibody (anti-H-2Ld). mAb to lymphocyte function-associated antigen does not inhibit cytotoxicity of the L3 clone against glial cells. Knowledge regarding the role of CTL within the CNS, including the surface molecules involved in glial cell lysis, could further the development of immunotherapies designed to effect immune reactivity within the CNS.
 ...
PMID:Susceptibility of astrocytes to class I MHC antigen-specific cytotoxicity. 310 79

Experimental Allergic Encephalomyelitis (EAE) was induced in rhesus monkeys by subcutaneous immunization with calfbrain homogenate in complete Freunds adjuvant. Monkeys were treated with major histocompatibility complex (MHC) Class II specific monoclonal antibodies (MoAb) as soon as the first clinical EAE signs became apparent. Two different treatments were tested. One consisted of 10 daily injections of a mixture of two MHC Class II specific MoAb, reactive with a monomorphic structure of rhesus monkey Class II molecules. The other consisted of 10 daily injections of Genox3.53, specific for HLA-DQW1. This MoAb crossreacts well with monkeys and also detects a polymorphism in this species and is presumably reactive with the RhLA-DQW1 antigen. Both MoAb treatments could modify the clinical course of EAE favourably. Untreated animals invariably died within 3 d of the onset of clinical EAE signs. Only one of the three monkeys treated with the monomorphic MHC Class II MoAb preparation died within 3 d, and the other two survived significantly longer than untreated animals. Both animals treated with Genox3.53 survived significantly longer than untreated control animals. Although only a few animals were tested, these results clearly show the possible beneficial influence of MHC Class II specific MoAb on a T-cell mediated autoimmune disease.
 ...
PMID:Successful treatment of EAE in rhesus monkeys with MHC class II specific monoclonal antibodies. 325 83

Localization of bone marrow-originated cells in the central nervous system (CNS) of the rat was investigated by using bone marrow chimeras. In order to do this, Lewis rats which carry major histocompatibility complex (MHC) class I antigens haplotype 1 (RT1.Al) were reconstituted with (Lew X PVG)F1 (RT1.Al/c) bone marrow cells after lethal irradiation. Transferred bone marrow cells were detected by immunohistochemical staining using a monoclonal antibody, OX27, specific for haplotype c of rat MHC class I antigens (RT1.Ac). The spleen and thymus of chimeric rats were fully reconstituted with transferred F1 cells 4 weeks after bone marrow transplantation. At this stage, mononuclear cells in the subarachnoid space of the CNS expressed OX27 antigen indicating that they were of bone marrow origin. A few OX27-positive blood cells were scattered in the CNS parenchyma 4-12 weeks after reconstitution. Ramified microglia, however, remained OX27-negative. Bone marrow-derived microglia were not observed throughout the period of examination until 24 weeks. In addition, experimental allergic encephalomyelitis (EAE) was induced in chimeric rats in order to augment the expression of MHC class I antigens on microglia. Even under this condition, no OX27-positive microglia were observed. Taken together, ramified microglia might be of neuroectodermal origin and there is little possibility that the microglia are derived from the bone marrow. However, if the ramified microglia are derived from blood cells, the microglia may be expected to have characteristic cell kinetics from the following points: (1) the precursor cells of the microglia may enter the CNS only at the perinatal stage; and (2) even under the condition in which lymphocytes and macrophages enter the CNS as observed in EAE, the precursor cells of the microglia are not supplied from the blood.
 ...
PMID:Absence of donor-type major histocompatibility complex class I antigen-bearing microglia in the rat central nervous system of radiation bone marrow chimeras. 331 71

In vivo administration of monoclonal antibody reactive with major histocompatibility complex-encoded Ia molecules (I-As) partially suppressed inflammation and demyelination in the spinal cord of SJL/J (H-2s) mice persistently infected with Theiler's murine encephalomyelitis virus. Demyelination was decreased if antibody was given at the time of virus inoculation or after inflammation had been established in the spinal cord. The decrease in demyelination was independent of isolation of infectious virus from the CNS or of serum titers of immunoglobulin to purified viral antigen. Thus, Theiler's virus-induced demyelination is mediated, in part, by immune cells that carry Ia class II molecules.
 ...
PMID:Partial suppression of Theiler's virus-induced demyelination in vivo by administration of monoclonal antibodies to immune-response gene products (Ia antigens). 348 48

To determine in situ localization of cells bearing major histocompatibility complex (MHC) class I or II antigens in the central nervous system (CNS), immunohistochemical examination was performed on CNS sections of Lewis rats sensitized for experimental allergic encephalomyelitis (EAE). Class I antigens identified by OX18 were detected on endothelial cells (EC) and cells with dendritic morphology (DC) of normal rats. OX18+ DC increased in number as the clinical signs of EAE became more severe, while the number of OX18+ EC in clinical EAE rats was not different from that of normal control rats. Infiltrating lymphocytes were always observed around OX18+ vessels. Double staining showed that OX18+ DC was negative for glial fibrillary acidic protein (GFAP). Cells with morphological features of oligodendroglia were not detected with OX18 in both normal control and EAE rats. MHC class II antigens (Ia antigens) were detected using three MAbs: OX3, OX6 and OX17. These three different MAbs essentially showed the same staining pattern. In normal controls, mononuclear cells in the subarachnoid space were stained positively, but no Ia+ parenchymal cells were detected. In EAE rats, Ia+ DC were first detectable in the white matter of the spinal cord at the preclinical stage, and increased in number as the disease progressed. On the other hand, double-staining with OX6 and anti-factor VIII-related antigen antiserum, or with OX3 and anti-vimentin antiserum demonstrated that endothelial cells even with lymphocyte cuffing were negative for Ia antigens. Based on the data obtained in the present study, the possible role of MHC class I and II antigens in the development of EAE is discussed.
 ...
PMID:In situ detection of class I and II major histocompatibility complex antigens in the rat central nervous system during experimental allergic encephalomyelitis. An immunohistochemical study. 348 35

Susceptibility to demyelination caused by the WW isolate of Theiler's murine encephalomyelitis viruses is linked to class II genes of the major histocompatibility complex. SJL/J (H-2s) mice, expressing only I-As class II gene products of the major histocompatibility complex, are highly susceptible to Theiler's murine encephalomyelitis virus infection with the WW virus isolate, with chronic paralysis and severe inflammation and demyelination in the central nervous system. The effect of in vivo administration of anti-I-As monoclonal antibodies on Theiler's murine encephalomyelitis virus infection was observed. SJL/J mice were treated in various protocols pre- or postinfection. Anti-I-As monoclonal antibody reversed chronic paralysis and reduced inflammation and demyelination when given after the establishment of persistent infection. The effect was long lasting, but clinical signs, inflammation, and demyelination recurred 2 months after treatment ceased. Anti-I-As antibodies had no effect on viral titers within the central nervous system. The timing of the administration of monoclonal antibodies was critical. Administration of anti-I-As before the establishment of the persistent infection resulted in fatal encephalitis.
 ...
PMID:Monoclonal anti-I-A antibody reverses chronic paralysis and demyelination in Theiler's virus-infected mice: critical importance of timing of treatment. 349 12


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