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)

T cells were directly cloned from autopsied MS brain plaque tissue and reactivity was measured with the major encephalitogenic neuroantigens, myelin basic protein (MBP), and proteolipid protein (PLP). Control clones were simultaneously derived from the blood. The proportion of T4+ and T8+ T cell clones from the brain tissue differed from that of peripheral blood T cell clones derived at the same time, suggesting that the clones were not derived from the peripheral blood. None of 57 brain-derived T cell clones proliferated to either MBP or PLP, although they responded well to PHA and IL 2. An additional 235 clones derived from the cerebrospinal fluid and 126 clones from the peripheral blood of other subjects with multiple sclerosis also did not proliferate to MBP or PLP. In contrast, five of nine T4+ clones from the CSF of a subject with postinfectious encephalomyelitis exhibited low but clear reactivity to human MBP, supporting the possible role of MBP as the target antigen in this disease. These studies, the first to clone T cells directly from MS plaque tissue, suggest that the lack of consistent T cell reactivity to MBP or PLP in the peripheral blood of MS patients does not appear to be secondary to the sequestration of a large number of these cells in the brain.
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PMID:Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis. 243 52

Theiler's murine encephalomyelitis virus (TMEV) is an enteric pathogen of mice which causes acute and chronic neurological disorders in the natural host. When brain-derived stocks of TMEV isolates are adapted to cell culture they predominantly form either large or small plaques. In this study the type of central nervous system (CNS) infection (acute versus chronic) and the associated disease occurring in mice inoculated intracerebrally with large and small plaque strains of TMEV was investigated. Large and small plaque strains of TMEV were found to vary in virulence, type of neurological disease produced and ability to establish persistent CNS infection in mice. Two large plaque strains, GDVII and FA viruses, were highly virulent, produced acute encephalitis, but were cleared from the nervous systems of surviving animals. Therefore, it appears that these large plaque variants do not cause persistent CNS infection in mice. In contrast, five small plaque strains, DA, WW, TO4, Yale and BeAn8386 viruses, were relatively avirulent, usually produced no illness during the first month after inoculation, but readily established persistent CNS infection in mice. Persistently infected mice later developed demyelinating disease. Having identified strains of TMEV that differ regarding their ability to persist, we now hope to be able to exploit this difference in elucidating the basic mechanism(s) of TMEV persistence.
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PMID:Persistent Theiler's murine encephalomyelitis virus infection in mice depends on plaque size. 624 40

The appearance of histological lesions and the localization of viral RNA in the central nervous system of mice infected with tissue culture-adapted Theiler's murine encephalomyelitis virus (WW strain) (TMEV-WW) was studied. Viral RNA was detected by autoradiography after in situ hybridization, using a (3)H-labeled DNA probe complementary to virion RNA, which was applied to deparaffinized sections of central nervous system tissues from infected mice. Subjacent histological sections of tissues were used to assess the location and extent of lesions. Lesions were first observed at 20 days post-inoculation and appeared to enlarge throughout infection. They consisted of infiltrates of mononuclear cells and lymphocytes in spinal cord white matter and leptomeninges; at 78 days post-inoculation severe necrotizing and demyelinative myelitis and gliosis were observed. In contrast to the pathogenesis of brain-derived TMEV-WW-infected mice, no lesions were found in the central nervous system gray matter of mice infected with tissue culture-adapted TMEV-WW at any time post-infection. Tissue culture-adapted viral RNA was found in the cells of spinal cord white matter throughout infection; only one neuron in close proximity to the injection site was found to contain viral RNA shortly after infection. At early times after infection, spinal cord white matter cells containing viral RNA were found before development of inflammatory lesions; at later days post-inoculation, positive cells were found within, at the periphery of, or at a distance from lesions. The number of infected cells and the amount of viral RNA per cell appeared to remain constant from 20 to 78 days post-inoculation despite the increasing intensity of the inflammatory response. The nearly exclusive spinal cord white matter tropism of tissue culture-adapted TMEV-WW appeared to directly correlate with the disease-inducing potential of this virus.
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PMID:Detection of tissue culture-adapted Theiler's virus RNA in spinal cord white matter cells throughout infection. 711 55

Tumor necrosis factor-alpha (TNF-alpha) has attracted the greatest attention as a major factor in experimental autoimmune encephalomyelitis (EAE) pathogenesis. We compared rats undergoing EAE with manipulated but healthy animals by examining TNF-alpha gene expression in cells recovered from the brain. We used reverse transcriptase-polymerase chain reaction (RT-PCR) as a sensitive assay for detection and Northern blot hybridization as a reliable quantitative assay of TNF-alpha mRNA. TNF-alpha gene expression was consistently detected in rats immunized with myelin basic protein (MBP) emulsified in complete Freund adjuvant (CFA), but not in rats immunized with MBP emulsified in incomplete Freund adjuvant (IFA), which does not induce EAE. Similarly, brain-derived cells from rats injected with cloned encephalitogenic T cells contained increased amounts of TNF-alpha mRNA compared with rats injected with nonencephalitogenic T cell clones similar in antigen specificity and in vitro lymphokine-producing capacity. Considering that the differing pathogenic capacity of MBP-reactive T cells might result from differing patterns of interaction with glia, we examined the impact of T-cell-glia interaction in vitro on cytokine gene expression in both cell types. Glial components were efficient in inducing TNF-alpha expression in T cells; T cells and T-cell-derived cytokines could elicit expression of several lymphokine genes in glial cells. Comparison of RT-PCR and blot hybridization assays, however, suggested that cytokine expression was much more efficient, on a per cell basis, in T cells than in glia. TNF-alpha was shown to have direct cytotoxic effect on glial cells, which was greatly enhanced by small amounts of interferon-gamma (IFN-gamma).
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PMID:Production of tumor necrosis factor-alpha as a result of glia-T-cell interaction correlates with the pathogenic activity of myelin basic protein-reactive T cells in experimental autoimmune encephalomyelitis. 887

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

In experimental autoimmune encephalomyelitis (EAE), CD4(+) self-reactive T cells target myelin components of the CNS. However, the consequences of an autoaggressive T cell response against myelin for neurons are currently unknown. We herein demonstrate that EAE induced by active immunization with an encephalitogenic myelin basic protein peptide dramatically reduces the loss of spinal motoneurons after ventral root avulsion in rats. Both brain-derived neurotophic factor (BDNF)- and neurotrophin-3 (NT-3)-like immunoreactivities were detected in mainly T and natural killer (NK) cells in the spinal cord. In addition, very high levels of BDNF, NT-3, and glial cell line-derived neurotrophic factor mRNAs were present in T and NK cell populations infiltrating the CNS. Interestingly, bystander recruited NK and T cells displayed similar or higher neurotrophic factor levels compared with the EAE disease-driving encephalitogenic T cell population. High levels of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNAs were also detected, and both these cytokines can be harmful to several types of CNS cells, including neurons. However, treatment of embryonic motoneuron cultures with TNF-alpha or IFN-gamma only had a deleterious effect in cultures deprived of neurotrophic factors. These results suggest that the potentially neurodamaging consequences of severe CNS inflammation are curbed by the production of several potent neurotrophic factors in leukocytes.
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PMID:Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells. 1088 12

Rabies is a fatal encephalomyelitis. Most cases occur in developing countries and are transmitted by dogs. Because of their high cost, cell culture vaccines have not totally replaced the unsafe brain-derived vaccines which are still used in many developing countries. Moreover, there will be a need for vaccines against rabies-related viruses against which classical vaccines are not always effective. DNA vaccines would, therefore, be a valuable alternative for the production of cheaper rabies vaccines against a larger spectrum of viruses. In this review we report published data on DNA-based immunization with sequences encoding rabies and rabies-related virus antigens.
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PMID:DNA-based immunization against Lyssaviruses. 1125 86

Chronic relapsing-remitting experimental autoimmune encephalomyelitis (CREAE) induced with myelin oligodendrocyte glycoprotein peptides 35-55 (MOG(35-55)) in NOD mice was successfully treated with brain-derived gangliosides (GA). The GA treatment suppressed the development and severity of CREAE, both clinically and histologically. Spleen cells from the GA-treated mice displayed markedly inhibited levels of MOG(35-55) specific proliferation and interferon-gamma production. Delayed-type hypersensitivity reactions to MOG(35-55) were suppressed by the GA treatment. GA modulate various T cell effector functions in CREAE and may be an effective therapeutic agent for autoimmune demyelinating diseases such as multiple sclerosis.
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PMID:Brain-derived gangliosides suppress the chronic relapsing-remitting experimental autoimmune encephalomyelitis in NOD mice induced with myelin oligodendrocyte glycoprotein peptide. 1143 74

The BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) persists in the CNS and produces a chronic inflammatory demyelinating disease that is an animal model for human multiple sclerosis (MS). The mechanisms leading to TMEV-induced demyelination are still under study but most likely involve both immune-mediated and virus induced damage to cells in the CNS, both depending on viral persistence. It is therefore important to identify the cells in which continued virus production is permitted. In this study, we looked at virus infection in primary astrocytes, microglia and oligodendrocytes, derived from brains of neonatal susceptible SJL/J mice. As evidenced by Western blots and immunocytochemistry, we were able to detect viral antigens in all these brain-derived cells. In addition, we extended the study to spinal cord tissues from mice suffering TMEV-induced disease. Immunohistochemistry staining with anti-TMEV sera and antibodies to specific cell markers detected viral antigens in all these cells. We then asked the question whether viral antigen present in these cells, particularly in microglia/macrophages, represented true viral replication or not. By using different techniques, including immunoprecipitation experiments and the very sensitive method of negative RNA detection through RNase protection assay, we show that both astrocytes and oligodendroglia permit de novo viral replication and viral protein synthesis but with only minimal cytopathic effects. Of these two cell types, astrocytes carry the brunt of viral replication. In microglia, on the other hand, viral replication is restricted since only minimal amounts of negative RNA copies can be demonstrated, while there are clear signs that some of these cells undergo apoptosis. These findings show that the main cell for viral replication is the astrocyte, rather than the microglia/macrophage. Most of the viral antigen present in macrophages, therefore, is probably the result of phagocytosis, rather than actual viral replication. In view of the demonstrated presence of viral replication in astrocytes and of great amounts of viral antigens in microglia/macrophages, it is possible that both types of cells act as antigen presenting cells during this immunopathological disease.
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PMID:Astrocytes, not microglia, are the main cells responsible for viral persistence in Theiler's murine encephalomyelitis virus infection leading to demyelination. 1202 Sep 50

Dendritic cells are thought to regulate tolerance induction vs immunization by transferring Ags and peripheral signals to draining lymph nodes (LN). However, whether myelin Ag transfer and presentation in LN occurs during demyelinating brain disease is unknown. In this study, we demonstrate redistribution of autoantigens from brain lesions to cervical LN in monkey experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Immunohistochemical analysis revealed significantly more cells containing myelin Ags in cervical LN of monkeys with EAE compared with those of healthy control monkeys. Myelin Ags were observed in cells expressing dendritic cell/macrophage-specific markers, MHC class II, and costimulatory molecules. Moreover, these cells were directly juxtaposed to T cells, suggesting that cognate interactions between myelin-containing APC and T cells are taking place in brain-draining LN. Indeed, myelin Ag-reactive T cells were observed in cervical LN from marmosets and rhesus monkeys. Importantly, these findings were paralleled by our findings in human tissue. We observed significantly more myelin Ag-containing cells in LN of individuals with MS compared with those of control individuals. These cells expressed APC markers, as observed in marmosets and rhesus monkeys. These findings suggest that during MS and EAE, modulation of T cell reactivity against brain-derived Ags also takes place in cervical LN and not necessarily inside the brain. A major implication is that novel therapeutic strategies may be targeted to peripheral events, thereby circumventing the blood-brain barrier.
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PMID:Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. 1242 16


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