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 examined T cells isolated from an autoimmune tissue lesion and from lymphoid organs for their ability to secrete tumor necrosis factor-alpha (TNF-alpha) and to adhere to extracellular matrix (ECM) proteins. CD4+ T cells were obtained from spleens, popliteal lymph nodes, and spinal cords of Lewis rats that had been immunized with myelin basic protein (MBP) to induce experimental autoimmune encephalomyelitis (EAE). We now report that, irrespective of whether or not the T cells were activated with MBP or the T cell mitogen concanavalin A (ConA), the T cells isolated from the spinal cord lesions secreted greater amounts of TNF-alpha and adhered better to ECM than did T cells from the draining lymph node. Thus, the lesions of EAE concentrate a subpopulation of CD4+ T cells with enhanced ability to interact with blood vessel wall components and to secrete TNF-alpha.
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PMID:T cells in the spinal cord in experimental autoimmune encephalomyelitis are matrix adherent and secrete tumor necrosis factor alpha. 137 27

Experimental allergic encephalomyelitis (EAE) is an autoimmune demyelinating disease of the central nervous system (CNS). EAE can be induced by immunization with myelin basic protein (MBP) or passive transfer of MBP-reactive T cell lines and clones. We established several T-cell clones from SJL/J mice by immunization with whole rat MBP or a synthetic peptide encompassing guinea pig MBP 89-101 which contains the encephalitogenic determinant for SJL/J mice. One clone was found to have lost its encephalitogenicity during long-term passages in vitro, although this clone maintains its specific reactivity to the encephalitogenic determinant. To clarify the difference between the encephalitogenic T cell clone (4b. 14a) and the non-encephalitogenic T-cell clone (4b. 14a/n), we examined the suppressive activity of 4b. 14a/n on the reactivity to antigen of 4b. 14a, various lymphokine production and adhesion molecules expression of 4b. 14a and 4b. 14a/n. The culture fluid of the both 4b. 14a/n and 4b. 14a revealed a suppressive effect on the proliferation of 4b. 14a stimulated by MBP 89-101, and the effect was not different between these clones. In lymphokine production, the activities of lymphotoxin, interferon or interleukin-2 were not different between encephalitogenic clones (4b.14a and TNT-1) and 4b. 14a/n, whereas the activity of tumor necrosis factor-alpha, passively secreted by antigen presenting cell, was higher in culture media of 4b. 14a/n. Examination of adhesion molecule expression of 4b.14a/n failed to show any differences in expression of lymphocyte function-associated antigen-1 (LFA-1) alpha and CD2 in the comparison with 4b. 14a. However, LFA-1 beta expression of 4b. 14a/n was always less than of 4b. 14a. The present studies indicated that the lack of encephalitogenicity of T-cell clones which were responsive to an encephalitogenic determinant depends not on the difference in major lymphokines production but partially on adhesion molecules expression which was decreased in non-encephalitogenic T-cell clone.
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PMID:[Experimental allergic encephalomyelitis: immunopathological analysis of antigenic reactivity and loss of encephalitogenicity]. 138 88

Previous research has shown that the dual cyclo-oxygenase and 5-lipoxygenase inhibitor, BW755c suppresses experimental autoimmune encephalomyelitis (EAE). In the present study, the effects of BW755c on both actively and passively induced EAE in the Lewis rat were examined, and also its effect on the accumulation of radiolabeled spleen cells in response to direct injection of tumor necrosis factor into the spinal cord. It was found that BW755c suppressed actively induced EAE but not passively induced EAE nor cytokine-induced cell accumulation in the central nervous system. It is concluded that arachidonic acid metabolites may be important in the induction phase of EAE, but do not appear to be crucial to the effector phase of EAE.
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PMID:Suppression of active but not passive autoimmune encephalomyelitis by dual cyclo-oxygenase and 5-lipoxygenase inhibition. 157 3

The expression of a battery of adhesion-related molecules and cytokines was investigated by immunocytochemistry in the central nervous system (CNS) of SJL/J mice sensitized for experimental autoimmune encephalomyelitis (EAE). These molecules consisted of the ligands MECA-325, intercellular adhesion molecule-1, and major histocompatibility complex molecules I and II, plus the receptors lymphocyte function-associated antigen-1, CD8, and CD4. The cytokines comprised interferon-gamma and tumor necrosis factor-alpha. EAE was induced by the adoptive transfer of myelin basic protein-sensitized lymphocytes. MECA-325, a marker for murine high endothelial venules in lymph node tissue, was absent from normal CNS tissue, was expressed at low levels on venules 24 to 48 hours before the onset of clinical signs, rose to maximal levels during acute disease, decreased to preclinical levels during remissions, and rose again during relapses. Intercellular adhesion molecule-1, major histocompatibility antigen-I, and major histocompatibility antigen-II showed similar fluctuations around CNS vessels. The receptors lymphocyte function-associated antigen-1 and CD4 fluctuated in parallel with the above molecules, whereas CD8 remained at a similar low level. Interferon-gamma was present during the acute, remitting, and relapsing phases and was localized to inflammatory cells, whereas tumor necrosis factor occurred at low levels only. Thus, several molecules associated with lymphocyte traffic in lymphoid tissue are selectively expressed in a stage-specific manner within the target organ, the CNS, during EAE. This suggests that the CNS may act as an ancillary organ of the immune system, and that cellular traffic into the CNS during EAE is related to the fluctuating expression of several distinct adhesion-related molecules, frequently co-expressed on the same vessel. The findings may have relevance to the sequence of events in the developing CNS lesion of multiple sclerosis.
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PMID:Adhesion-related molecules in the central nervous system. Upregulation correlates with inflammatory cell influx during relapsing experimental autoimmune encephalomyelitis. 167 55

Among the myelin basic protein (MBP)-specific T-cell clones mediating experimental allergic encephalomyelitis (EAE), which were established from SJL/J mice, one clone was found to have lost its encephalitogenicity during long-term passages in vitro, although the clone keeps its specific reactivity to the encephalitogenic determinant lying in the sequence of guinea pig MBP 89-101. To clarify the difference between the encephalitogenic T-cell clone (4b.14a) and non-encephalitogenic T-cell clone (4b.14a/n), we examined various lymphokines secreted into the culture media of 4b.14a and 4b.14a/n. The results show that the activities of lymphotoxin, interferon-gamma or interleukin-2 were not different between encephalitogenic clones and 4b.14a/n, whereas the activity of tumor necrosis factor-alpha, possibly secreted from antigen-presenting cells, was higher in culture media of 4b.14a/n. Moreover, the culture fluid of both 4b.14a/n and 4b.14a revealed suppressive effect on the proliferation of 4b.14a stimulated by MBP 89-101, but the effect was not different between the two clones. Thus, it is suggested that neither production of lymphokines examined so far nor soluble suppressive substance is related to the loss of encephalitogenicity of the T-cell clone.
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PMID:Lymphokine production by encephalitogenic and non-encephalitogenic T-cell clones reactive to the same antigenic determinant. 169 73

To define a role for the cytokine tumor necrosis factor (TNF) in immune-mediated demyelination, the effect of anti-TNF antibody was investigated with a form of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice induced by the adoptive transfer of myelin basic protein-(MBP)-sensitized T lymphocytes, an animal model of the human disease multiple sclerosis (MS). In three separate experiments, no mouse sensitized for EAE and then treated with anti-TNF by intraperitoneal injection developed signs of central nervous system (CNS) disease. Examination of CNS tissue from anti-TNF-treated animals showed no pathological changes. CNS tissue from control animals demonstrated extensive inflammatory cell infiltration and demyelination. To test whether anti-TNF therapy was inhibitory to encephalitogenic cells, preincubation of MBP-sensitized T lymphocytes with anti-TNF in vitro prior to injection into recipient mice was performed, and resulted in no diminution of their ability to transfer EAE. In addition, spleen cells from anti-TNF-treated mice were capable of serial transfer of EAE, similar to spleen cells from control animals. However, spleen cells from anti-TNF-treated mice did not produce TNF on stimulation with MBP or concanavalin A. This study showed that anti-TNF antibody can inhibit effectively the development of EAE by interfering with the effector, rather than the induction, phase of the disease. Anticytokine therapy may have important applications in the development of new therapeutic strategies for MS.
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PMID:Anti-tumor necrosis factor therapy abrogates autoimmune demyelination. 172 88

The effect of human recombinant tumor necrosis factor-alpha (TNF) on experimental allergic encephalomyelitis (EAE) was studied in Lewis rats. TNF was injected intraperitoneally at a daily dose of 1 x 10(3) or 2 x 10(4) U for 8 consecutive days from one day after sensitization with guinea-pig spinal cord in complete Freund's adjuvant. All rats in the control group developed clinical signs of EAE but recovered within 8 days after the onset. Injections of 2 x 10(4) U/day of TNF resulted in a significant prolongation of clinical EAE: clinical signs were sustained for up to 15 days after onset. Histologically, rats receiving 2 x 10(4) U/day of TNF had more severe cellular infiltrations in the spinal cord than controls. The augmentation of EAE was not found in rats receiving 1 x 10(3) U/day of TNF or TNF that had been neutralized with anti-TNF monoclonal antibody.
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PMID:Human tumor necrosis factor-alpha augments experimental allergic encephalomyelitis in rats. 191 22

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

The role of tumor necrosis factor (TNF) was examined in the pathogenesis of actively induced experimental allergic orchitis (EAO) and experimental allergic encephalomyelitis (EAE) in the mouse. The ability of TNF to function as either an adjuvant or to replace pertussigen in eliciting active EAO was examined by treating groups of mice immunized for disease induction with 10 micrograms of recombinant murine TNF at various time points throughout both the induction and effector phases of the disease process. All groups of animals receiving TNF ranging from 2 days before antigen challenge to 26 days postimmunization failed to exhibit significant disease in comparison to animals treated with pertussigen, indicating that TNF can neither serve as an adjuvant nor replace pertussigen in eliciting active disease. Similarly, the role of TNF in the pathogenesis of EAO and EAE was investigated by examining the ability of a known neutralizing rabbit anti-TNF IgG antibody preparation to either inhibit the development or decrease the severity of the clinical symptoms and/or the inflammatory lesions associated with the disease processes. Groups of either B6AF1 hybrid or SJL/J mice were immunized for the induction of active EAO and EAE, respectively. They were passively immunized with either 2 mg of purified anti-TNF IgG or control anti-CFA IgG at time points ranging from 2 days before to 28 days after antigen challenge. All groups, regardless of the day of treatment with anti-TNF IgG, did not exhibit a markedly significant difference in disease outcome in comparison to either groups receiving no antibody or passively immunized with anti-CFA IgG. Taken together, these results suggest that TNF does not appear to be the principal cytokine/lymphokine involved in the pathogenesis of actively induced EAO and EAE.
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PMID:An analysis of the role of tumor necrosis factor in the phenotypic expression of actively induced experimental allergic orchitis and experimental allergic encephalomyelitis. 230 44

Myelin basic protein (MBP)-specific T cell lines derived from SJL mice lose the ability to transfer adoptively experimental allergic encephalomyelitis (EAE) after 5-6 restimulations with antigen in vitro. In order to test whether such lines were suppressive, non-encephalitogenic T cell lines were co-cultured with a freshly derived encephalitogenic T cell line. Following co-culture in the presence of MBP and irradiated syngeneic spleen cells the mixture was transferred adoptively to syngeneic recipients. Severe EAE was observed in recipients of the encephalitogenic cell line alone but not in animals which received the co-culture. A co-culture period was required as mixing the encephalitogenic and non-encephalitogenic T cell lines just prior to transfer was without effect. Not all non-encephalitogenic cell lines were found to be suppressive. Culture fluids from the suppressive, but not the non-suppressive lines were found to inhibit MBP-driven proliferation of T cell clones and encephalitogenic lines in vitro. Nineteen of 55 MBP-specific T cell clones derived from suppressive lines were found to elaborate the suppressive supernatant activity. The suppressive effect was not antigen-specific since the same culture supernatants inhibited proliferation of an ovalbumin-specific SJL T cell clone. The suppressive effect became apparent only after T cell lines had lost encephalitogenicity and was not mediated by tumor necrosis factor, lymphotoxin or prostaglandin.
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PMID:Suppressive activity of long-term myelin basic protein-specific SJL T cell lines. 247 98


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