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)

Embryonic brain tissue allografts under many circumstances survive transplantation into the brain. It is generally believed that such grafts will not survive if the host animal is systemically sensitized, by skin grafting or other means, to major histocompatibility complex (MHC) antigens of the donor animal. We have found that F344 brain grafts survive in BN hosts even when the host is systemically sensitized to F344 tissue. Embryonic cerebral neocortex from F344 donors was transplanted into BN host rats (n = 95). Subsequently, the host rats were systemically sensitized with donor skin (n = 25), brain tissue (n = 41), or spleen cells (n = 6) and compared with a control group of rats consisting of allografts with no sensitization or sham procedures (n = 23). Rejection of the transplants in BN rat hosts was not provoked by any of the sensitization methods tested. Minor immunological responses that did not result in rejection were, however, present in many host animals. We did not observe infiltration of W3/13+ T cells and OX8+ cytotoxic lymphocytes in any of the groups. Nevertheless, substantial infiltrations of OX6+ antigen-presenting cells and W3/25+ helper T cells were present. There was also an extensive enhancement of MHC class I immunoreactivity in parts of the grafted tissue developing within the third ventricle, but not for the same type of graft in the lateral ventricle. This increase of MHC class I expression was not accompanied by infiltration of cytotoxic T cells. Our findings thus suggest that neural graft rejection depends on general genetic susceptibility to immune reactions, particularly experimental allergic encephalomyelitis and not only on disparity between donor and host antigens encoded by the MHC. Moreover, enhancement of MHC class I and class II expression within transplanted tissue does not predict graft rejection.
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PMID:BN rats do not reject F344 brain allografts even after systemic sensitization. 192 9

Immunoelectron microscopical techniques have been used to study class II major histocompatibility complex (MHC) expression by cells in the spinal cords of Biozzi AB/H mice with chronic relapsing experimental allergic encephalomyelitis. Throughout the course of disease both astrocytes and endothelia failed to express significant levels of class II MHC antigens. The major central nervous system resident cell types found to express class II MHC antigens were the perivascular microglia, with infiltrating macrophages and some lymphocytes being strongly positive.
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PMID:An immunoelectron microscopical study of the expression of class II major histocompatibility complex during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice. 205 70

Over the past decade monoclonal antibodies have been successfully employed in a number of animal models of autoimmune disease. We have used antibodies to the class II gene products of the major histocompatibility complex, the CD4 molecule on helper T cells, and the T-cell receptor. Monoclonal anti-class II antibodies have been administered to treat paralytic disease in the animal model of multiple sclerosis--experimental allergic encephalomyelitis. These antibodies not only reverse acute paralytic disease but also decrease the number of relapses in a model of relapsing/remitting multiple sclerosis when given after the first attack. The advantage of this form of therapy is that it is haplotype specific. In other words, in a heterozygous individual it is possible to block the major histocompatibility gene associated with disease susceptibility while leaving other major histocompatibility gene products free for antigen presentation. Thus, animals given this form of immunotherapy are not significantly immunosuppressed. Antibodies to the CD4 molecule have been equally effective in treating animal models of autoimmunity. We and others have reversed ongoing paralysis in experimental autoimmune encephalomyelitis. Relapses have been diminished after the administration of anti-CD4. Antibodies to CD4 have been used successfully to treat animal models of systemic lupus erythematosus, rheumatoid arthritis and myasthenia gravis. Recent trials with anti-CD4 have been successful in the treatment of rheumatoid arthritis and cutaneous T-cell lymphoma. The latter trial employed a chimeric human/mouse antibody. Antibodies to the variable region of the T-cell receptor have been employed to treat experimental autoimmune encephalomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The use of monoclonal antibodies for treatment of autoimmune disease. 208 87

The transforming growth factors (TGF) type beta 1 and beta 2 are regulatory cytokines strongly affecting rat astrocyte immune functions. Both cytokines suppressed presentation of autoantigen by astrocytes: highly encephalitogenic T cells cocultured with TGF-beta-treated astrocytes in the presence of myelin basic protein did not become activated to transfer experimental allergic encephalomyelitis, a central nervous system (CNS) autoimmune disease. Furthermore, TGF-beta 1 and -beta 2 antagonized hyperinduction of astrocyte major histocompatibility complex (MHC) class II antigen expression by interferon-gamma and tumor necrosis factor-alpha. Thus, TGF-beta might be a potential regulator of CNS inflammation.
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PMID:Transforming growth factors type beta 1 and beta 2 suppress rat astrocyte autoantigen presentation and antagonize hyperinduction of class II major histocompatibility complex antigen expression by interferon-gamma and tumor necrosis factor-alpha. 210 88

Intrathecal injection of interferon-gamma induced a significant increase of the number of class I and class II major histocompatibility complex (MHC)-expressing cells within the rat nervous system. A progressive appearance of MHC-antigen-positive cells was found by light- and electron microscopic immune histology. The first level comprised cells that constitutively expressed MHC antigens in normal animals (meningeal and endoneural monocytes, some perivascular dendritic cells, and few parenchymal microglia cells, especially in the lumbar spinal cord and in the cerebellar white matter). The second level represented cells readily expressing MHC antigens after stimulation with interferon-gamma (all perivascular, dendritic cells, and microglia). The third level included ependymal cells, astrocytes, and Schwann cells. After stimulation with interferon-gamma, these neuroectodermal cells expressed MHC antigens inconsistently, usually in a low density and patchy distribution. The progressive appearance of MHC antigens may be reflected by the variances of lesional patterns found in experimental allergic encephalomyelitis of different histologic severity.
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PMID:Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system. 212 Oct 41

Embryonic rat hippocampal primordia from class I and class II major histoincompatible donors were transplanted into the hippocampus of adult rat hosts. The allografts were rejected by a specific host immune response, which was identified by reference to events at a histocompatible hippocampal primordial graft (syngeneic to the host) of similar embryonic age placed simultaneously in the contralateral hippocampus of the same hosts. The present combined light immunohistochemical and electron microscopic study was undertaken to elucidate the mechanism of induction of the immune response by a graft of a tissue which does not constitutively express major histocompatibility antigens, to identify which cells are involved, and how they enter the brain and attack the graft, and to look for possible sources of variability in the outcome of such an attack. Our main findings are (1) that host and graft microglia play a prominent role from the earliest stages, and throughout the evolution of the histological changes, (2) that the later entry of host dendritic cells, lymphocytes, and lymphoblasts (with associated mitoses) into the perivascular cuffs of the graft vasculature ensures that the local immune response becomes self-propagating, (3) that the allografted neurons are killed by host cytotoxic lymphocytes only after a previous encirclement by host macrophage-derived microglial cells, and (4) that the observed variability (especially within different regions of a single allograft) is associated not with failure of immune induction, but with local failure of the graft tissues to express allotypic major histocompatibility antigens. Our observations confirm that once the host immune system has been primed, local factors leading to the induction of transplant major histocompatibility complex antigens make histoincompatible intracerebral transplants of embryonic into adult brain tissue vulnerable to vigorous and effective immune attack. The histological picture of the immune response observed in our intracerebral allografts resembles that described in intraventricular allografts of embryonic brain, in allografts of other organs and tissues such as skin, kidney, and heart, and also that seen in the response to brain autoantigens in multiple sclerosis and experimental allergic encephalomyelitis. However, the involvement of a special cell type, the perivascular microglial cell, in the early stages of immune induction in brain raises the possibility of designing future therapeutic approaches which might selectively block this step in conditions such as multiple sclerosis.
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PMID:Mechanisms of allograft rejection in the rat brain. 213 52

Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination.
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PMID:Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice. 221 25

Reversal of autoimmune disease with monoclonal antibodies to polymorphic determinants associated with class II gene products of the major histocompatibility complex (MHC) and to T-cell receptor variable region segments has been demonstrated in animal models. Recent studies have shown that it is also possible to use mutant peptides to block recognition of self-antigen associated with MHC by T-cells that mediate autoimmune disease. These mutant peptides have been used to prevent the model autoimmune condition experimental allergic encephalomyelitis. The possibility of extending these approaches to human disease is discussed.
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PMID:Development of antigen-specific therapies for autoimmune disease. 223 45

We have investigated the capacity of the lymphokine gamma-interferon (IFN-gamma) to induce class II major histocompatibility complex (MHC) antigens on astrocytes cultured from BALB/c mice. This is a mouse strain resistant to experimental allergic encephalomyelitis (EAE), and in a recent report Massa et al. (Proc. Natl. Acad. Sci. U.S.A., 84 (1987) 4219-4223) indicated that BALB/c astrocytes in vitro were not susceptible to class II MHC antigen induction by IFN-gamma. We observed, in agreement with this previous report, that when primary cultures of astrocytes from neonatal BALB/c mice were just at confluence (7-10 days in vitro), IFN-gamma did not stimulate expression of class II MHC antigens. However, after 14-16 days in vitro, a population of astrocytes emerged in the cultures on which class II MHC antigens could be induced. These cells expressed the astrocyte marker glial fibrillary acidic protein, and were found in close association to small round superficial cells (multipotential precursor cells), and to microglia. These results indicate that the ability of astrocytes to respond to lymphokine stimulation is not completely correlated with susceptibility to EAE, and further suggest the importance of central mechanisms in the development of inflammatory brain disease.
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PMID:Induction of class II major histocompatibility complex antigens on a population of astrocytes from a mouse strain (BALB/c) resistant to experimental allergic encephalomyelitis. 233 4

Experimental allergic encephalomyelitis (EAE) can be induced in some strains of rat but not others, by the injection of guinea-pig myelin basic protein in Freund's complete adjuvant. In the susceptible Lewis strain, spontaneous recovery from paralysis occurs and previous studies have shown that this recovery is dependent on the production, during the course of the disease, of high levels of corticosterone from the adrenal glands. Adrenalectomy completely abrogates the recovery phase and the disease becomes uniformly fatal unless steroid replacement therapy is given, which reproduces the serum levels of hormone that develop in intact animals with EAE. The PVG strain is not susceptible to EAE, but here it is shown that PVG rats that had been adrenalectomized developed severe disease from which they do not recover. As in the adrenalectomized Lewis rat, steroid replacement therapy could prevent the fatal outcome and in this case the disease course resembled that seen in intact Lewis animals. By a number of parameters PVG rats appear to make a more vigorous steroid response to stress than do Lewis. A comparison of the ratio of adrenal weight to body weight between these strains indicated that this ratio is larger in PVG, and serum corticosterone levels, in response to stress, were also found to be higher in this strain. Furthermore, basal levels of corticosterone were much more labile in PVG rats and had a higher mean value than those found in the age- and sex-matched Lewis animals with which they were compared. Genetic analysis using congenic rat strains showed that a high adrenal weight to body weight ratio was not linked to the major histocompatibility complex (MHC). It appears that the resistance to EAE of PVG rats depends on an enhanced stress response that mediates its immunosuppressive effect via the adrenal glands. While this stress response plays an essential part in the recovery of Lewis strain rats from EAE, it is sufficiently potent in PVG rats to virtually completely prevent signs of disease. Resistance to the induction of EAE could not be abrogated by adrenalectomy in all strains of rats studied. In particular, congenic PVG.RT1u rats, with the same background genes as PVG but with RT1u rather than the RT1cMHC genes of PVG, did not develop EAE when the adrenal glands were removed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of the neuroendocrine system in determining genetic susceptibility to experimental allergic encephalomyelitis in the rat. 235 53


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