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)

Experimental allergic encephalomyelitis (EAE) was generated in SJL and B10.PL mice by using the synthetic myelin basic protein peptides. Inflammation in brain and spinal cord preceded clinical signs of disease. Infiltrating lymphocytes were predominantly Lyt1+ (CD5+), L3T4+ (CD4+) T cells, until day 18. After that, F4/80+ monocyte/macrophages outnumbered T cells. Ia+ cells were microglia, macrophages, and endothelial cells, but Ia was not detectable on astrocytes in this EAE model. Ia+ endothelial cells appeared later in the disease than Ia+ microglia and macrophages, suggesting that antigen presentation at the blood-brain barrier is not initially responsible for inflammation. Cells staining for interferon gamma, interleukin 2 (IL-2), and IL-2 receptors were more prominent than IL-4, IL-5, lymphotoxin (LT), and tumor necrosis factor alpha (TNF-alpha), which occurred transiently in the second week and were associated with fewer cells. TNF-alpha and LT were never seen in spinal cord, suggesting that these cytokines are not responsible for initiation of clinical disease. Few or no cells stained for IL-6, IL-1, or transforming growth factor beta. Control animals injected with complete Freund's adjuvant in saline or control antigen demonstrated no inflammatory cell infiltration or cytokine production. Thus, our findings suggest a peptide-induced EAE model in which Th1 T-cell-macrophage interactions result in the disease process.
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PMID:Inflammatory leukocytes and cytokines in the peptide-induced disease of experimental allergic encephalomyelitis in SJL and B10.PL mice. 137 May 83

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

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

Lymphokine activity in seven myelin basic protein (MBP)-specific T cell clones was examined. All of the clones recognize MBP peptide 1-9 in the context of I-Au. A strong positive correlation was found between levels of lymphotoxin (LT) and tumor necrosis factor alpha (TNF-alpha) mRNA and biological activity on L929 cells and their capacity to induce paralysis, the clinical hallmark of experimental allergic encephalomyelitis (EAE). No correlation was found between interleukin-2 or gamma interferon production and encephalitogenicity. LT and/or TNF-alpha may play a central role in the pathogenesis of EAE.
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PMID:Lymphotoxin and tumor necrosis factor-alpha production by myelin basic protein-specific T cell clones correlates with encephalitogenicity. 170 60

Uncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, and AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor beta [TNF-beta]) and TNF-alpha in experimental allergic encephalomyelitis (EAE), a murine model of an autoimmune demyelinating disease. In this communication, we report that treatment of recipient mice with an antibody that neutralizes LT and TNF-alpha prevents transfer of clone-mediated EAE. LNC-8, a myelin basic protein-specific T cell line, produces high levels of LT and TNF-alpha after activation by concanavalin A, antibody to the CD-3 epsilon component of the T cell receptor, or myelin basic protein presented in the context of syngeneic spleen cells. LNC-8 cells transfer clinical signs of EAE. When LNC-8 recipient mice were also treated with TN3.19.12, a monoclonal antibody that neutralizes LT and TNF-alpha, the severity of the transferred EAE was reduced, while control antibodies did not alter the disease. The effect of anti-LT/TNF-alpha treatment was long lived and has been sustained for 5 mo. These findings suggest that LT and TNF-alpha and the T cells that produce them play an important role in EAE.
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PMID:An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. 221 48

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

NK cells mediate their cytotoxicity against tumor cells through abroad array of cytotoxic and cytostatic proteins. We investigated whether specific proteins could also be identified that contributed to NK cell-mediated antiviral immunity. Human CD16+/CD3- NK cells were obtained by using FACS and subsequently cloned by using limiting dilution. These NK cell lines, which were cytotoxic against NK-sensitive tumor targets and virally infected cells, also generated supernatants that selectively killed vesicular stomatitis virus-infected cells while sparing noninfected cells. This soluble antiviral activity was completely neutralized by antibodies specific for TNF and lymphotoxin. Purified human rTNF also duplicated this specific cytotoxicity against vesicular stomatitis virus-infected cells, as well as against CMV-, Theiler's murine encephalomyelitis virus-, and HSV-infected cells. The degree of cytotoxicity varied for the different viruses and depended on the cell type infected. These results suggest that NK cells can mediate selective and direct cytotoxicity against virally infected cells by the secretion of TNF and lymphotoxin.
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PMID:Tumor necrosis factor and lymphotoxin secretion by human natural killer cells leads to antiviral cytotoxicity. 284 93

A cytokine-mediated excessive increase in nitric oxide (NO) by macrophages or glial cells via an inducible isoform of NO synthase (iNOS) has been proposed to play an important role in demyelinating diseases. To further investigate the role of iNOS in demyelination, experimental allergic encephalomyelitis (EAE), a known animal model of multiple sclerosis (MS) in mice, was chosen in this study. A semiquantitative reverse transcriptase-polymerase chain reaction (RT/PCR) analysis revealed an increase in the mRNA levels of iNOS and cytokines known to induce iNOS or inflammatory cytokines (interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-6, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta) in the spinal cord corresponding to the severity of the disease without significant change in the mRNA levels of immunoregulatory cytokines (IL-4, IL-10 and transforming growth factor (TGF)-beta) during the course of EAE. An immunohistochemical examination of the spinal cord using an iNOS-specific antibody showed iNOS-positive cells to be mainly inflammatory cells with a higher frequency of iNOS-positive cells at the peak of EAE than in the early phase. These iNOS-positive cells at the peak appeared to be composed of infiltrating macrophages and most of them were located in the necrotic area. These results suggested that cytokine-induced excessive NO via iNOS by macrophages caused tissue damage in the central nervous system in EAE.
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PMID:Expression of the inducible isoform of nitric oxide synthase in the central nervous system of mice correlates with the severity of actively induced experimental allergic encephalomyelitis. 749 86

We previously reported that the CD4+ suppressor cells (Ts) that regulate recovery of Lewis rats from experimental autoimmune encephalomyelitis (EAE) produce transforming growth factor-beta (TGF-beta). We also reported that TGF-beta downregulates interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2) production, by the CD4+ effector T cells (Te) that mediate EAE. We now report that TGF-beta also inhibits the production of tumor necrosis factor/lymphotoxin (TNF/LT) by EAE effector cells. When activated in vitro with myelin basic protein (MBP), Te produced TNF/LT, as measured using a WEHI 164 cytotoxicity assay. The specificity of cytokine action was demonstrated using neutralizing antibodies to TNF/LT. When added to the Te+MBP cultures, TGF-beta inhibited TNF/LT production in a dose-dependent fashion. Moreover, neutralizing anti-TGF-beta antibodies augmented TNF/LT production in the Te+MBP cultures. We also confirm that TGF-beta inhibits adoptive transfer of EAE. In contrast, murine IL-10 only partially inhibited TNF/LT and IFN-gamma production by Te. We conclude that TGF-beta production by Ts plays a major role in recovery from EAE in the Lewis rat by inhibiting TNF/LT and IFN-gamma production by the effector cells that mediate EAE.
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PMID:Transforming growth factor-beta 1 inhibits tumor necrosis factor-alpha/lymphotoxin production and adoptive transfer of disease by effector cells of autoimmune encephalomyelitis. 751 80

Intravenous treatment of Lewis rats with neuroantigen-coupled splenocytes 7 days before the induction of experimental autoimmune encephalomyelitis with guinea pig myelin basic protein (GP-MBP) resulted in a significant reduction of both the incidence and severity of clinical disease. To test the epitope and functional specificities of the unresponsiveness, splenocytes (SP) coupled with the major encephalitogenic MBP determinant, GP-68-86, were compared with those coupled with intact GP-MBP for the ability to down-regulate clinical disease and Ag-specific T cell responses (proliferation, cytokine production, and delayed-type hypersensitivity) in animals primed with either intact GP-MBP/CFA or GP-68-86/CFA. GP-MBP-SP and GP-68-86-SP were equally efficient at significantly inhibiting clinical disease in animals primed with GP-68-86/CFA. In contrast, tolerization with intact GP-MBP-SP was significantly more efficient than that with GP-68-86-SP at reducing disease incidence and severity in GP-MBP/CFA-primed animals, which indicates a role for secondary (cryptic) encephalitogenic epitopes in GP-MBP-induced disease. By testing a panel of GP-68-86 peptides that contained conservative amino acid substitutions at either position 75 (A75) or 80 (P80) or at both, residues that previously had been shown to be TCR contact residues, for their ability to inhibit experimental autoimmune encephalomyelitis induction, were assessed for the fine specificity of tolerance induction. None of the substituted peptides were capable of affecting the course of paralytic disease that had been induced by sensitization with the native GP-68-86 epitope, but all significantly reduced a milder form of the disease that had been produced by priming with the (A75,P80) 68-86 substituted peptide. With regard to the functional specificity of tolerance induction, lymph node T cells derived from either GP-MBP-SP- or GP-68-86-SP-treated animals exhibited a marked reduction in both proliferation and production of Th1-derived cytokines (IL-2, IFN-gamma, and lymphotoxin/TNF-alpha) in response to either GP-MBP or GP-68-86 in culture. In contrast, no consistent significant differences in delayed-type hypersensitivity responses were observed in any of the experimental groups relative to controls. Histologic examination of central nervous system tissues from the tolerant and control groups revealed significantly reduced, but still demonstrable, levels of perivascular infiltration even in asymptomatic animals.
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PMID:Epitope and functional specificity of peripheral tolerance induction in experimental autoimmune encephalomyelitis in adult Lewis rats. 751 25


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