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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using experimental autoimmune encephalomyelitis (EAE) in the rat as a model of central nervous system (CNS) inflammation, activated and quiescent T lymphocytes with different antigen specificities were labelled with the fluorescent dye Hoechst 33342 and tested by fluorescence microscopy for their ability to accumulate in different regions of the spinal cord and in other organs at varying times post inoculation. With this highly sensitive assay it was found that activated myelin basic protein (MBP)-specific T cell lines accumulated in the spinal cord (a 1000-fold increase in the lumbar/sacral region by day 4) and caused clinical signs of EAE. In contrast, interleukin-2 (IL-2)-maintained (quiescent) MBP-specific T cell lines failed to accumulate in the CNS and cause disease. Activated ovalbumin (OA)-specific and purified protein derivative of tuberculin (PPD)-specific T cell lines were also found at significantly higher levels in the spinal cord than non-activated cells although they failed to accumulate to a substantial degree when injected alone. When injected with activated MBP-specific T cells the activated OA- and PPD-specific cell lines accumulated in the spinal cord following initial accumulation of the MBP-specific cells, demonstrating that during the inflammatory process there is considerable non-specific recruitment of cells into the inflammatory site. CNS accumulation of activated MBP-specific T cell lines occurred 1-2 days later in irradiated animals than in non-irradiated recipients. This was consistent with irradiated animals also exhibiting a later onset of disease and suggests that irradiation may directly affect the endothelium in a way that makes it less adhesive. In conclusion, this study demonstrates that activated lymphocytes of any specificity enter the spinal cord, and that the neuro-antigen specific cells accumulate there and lead to the recruitment of other cells. Non-activated cells, even those with neural antigen specificity fail to enter the cord. Understanding the nature of what an 'activated' lymphocyte is may allow us to design strategies to inhibit such immune-mediated inflammation.
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PMID:Selective localisation of neuro-specific T lymphocytes in the central nervous system. 137 55

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

In old BALB/c mice susceptibility to experimental allergic encephalomyelitis (EAE) with bovine proteolipid apoprotein (PLP) is reduced significantly. Eleven of 21 8-week BALB/c mice developed clinical signs of EAE following injection of PLP but only two of 18 12-month BALB/c mice and one of 19 24-month BALB/c mice showed clinical signs of EAE. Susceptibility to EAE induced by either PLP or bovine myelin basic protein (MBP) also was reduced in old SJL mice. However, the aging process had no effect on the clinical signs of EAE in both strains, if EAE appeared. Some old BALB/c mice developed histologic EAE with significant demyelination without clinical signs. Lymphocyte proliferative response to mitogens and antigens, and interleukin-2 (IL-2) production, also were depressed in the aged mice (24-month BALB/c and 18-month SJL) probably due to the functional defect of T cells, since the function of macrophages as antigen-presenting cells was not affected in the old mice. PLP-sensitized spleen cells (SPC) from 8-week mice were able to adoptively transfer EAE to young and aged recipients. PLP-sensitized T cells from 8-week mice, reconstituted with young or old monocytes, also were able to transfer EAE into young mice. In contrast, spleen cells from aged mice did not induce EAE, so the reduction of EAE susceptibility was mainly explained by the failure of T cell activity. This T cell defect was not restored by exogenous IL-2.
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PMID:Studies of experimental allergic encephalomyelitis in old mice. 169 15

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

IL2-PE40 is a chimeric protein composed of human interleukin-2 (IL2) genetically fused to a modified form of Pseudomonas exotoxin lacking the cell recognition domain. IL2-PE40 is cytotoxic for IL2 receptor-bearing lymphocytes in culture and can inhibit activation of T cells in vivo. IL2-PE40 can significantly diminish antigen-stimulated proliferation of lymphocytes sensitized to myelin basic protein. Intraperitoneal administration of IL2-PE40 not only markedly inhibits the clinical manifestations of adoptively transferred relapsing experimental allergic encephalomyelitis but also dramatically reduces both inflammation and demyelination characteristic of the disease.
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PMID:Chimeric cytotoxin IL2-PE40 inhibits relapsing experimental allergic encephalomyelitis. 170 44

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats and the bromodeoxyuridine (BrdU)-incorporating cells were demonstrated immunohistochemically in lesions in the central nervous system (CNS) to assess the extent of T cell proliferation during EAE. In active EAE, BrdU+ cells were most numerous on day 12 postimmunization, when both clinical signs and inflammation detected by histologic examination were most severe; they declined thereafter although a considerable number of inflammatory foci remained in some rats. In passive EAE, BrdU+ cells were most numerous 2 days before the full-blown EAE and then rapidly decreased in number. On day 6 post-transfer, the CNS showed the most severe histologic changes but virtually no inflammatory cells in the lesions were labeled with BrdU. Double immunofluorescence staining with T cell (OX52) and macrophage/microglia (OX42) markers showed that about half of the BrdU+ cells were labeled with OX52 at the peak of EAE. The proportion of BrdU+OX52+ T cells at later stages was about 20%. BrdU+OX42+ cells ranged between 50 and 80% throughout the course of the disease. Furthermore, serial pulsing experiments during passive EAE revealed that inflammatory cells that had been labeled with BrdU outside the CNS and found later in the CNS were 15 times more numerous than those labeled in situ in the CNS. Taken together, these findings indicate that the majority of T cells involved in EAE undergo DNA synthesis outside the CNS and then infiltrate into the CNS, and that T cells labeled in situ in the CNS are few, and decrease rapidly in number. Since interleukin-2-receptor-positive cells detected by mAb OX39 outnumbered BrdU+ T cells at these later stages, we postulate that an unresponsive state instead of T-cell proliferation was induced in the CNS.
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PMID:In situ demonstration of proliferating cells in the rat central nervous system during experimental autoimmune encephalomyelitis. Evidence suggesting that most infiltrating T cells do not proliferate in the target organ. 173 Nov 49

SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-interferon-gamma (IFN-gamma) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-gamma to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-gamma. These findings support the notion that IL-2 is required for disease induction whereas IFN-gamma plays a disease-limiting role early in the development of EAE.
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PMID:Effect of anti-interferon-gamma and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse. 173 76

Gliotoxin is a fungal metabolite belonging to the class of epipolythiodioxopiperazines which possesses both immunomodulating and anti-phagocytic activities. We have examined the effect of gliotoxin on passively induced allergic encephalomyelitis and report here that pulse treating activated experimental allergic encephalomyelitis (EAE) effector lymphocytes with gliotoxin inhibits, in a dose-dependent manner, their ability to transfer disease. Cells treated with 300 ng/ml are unable to replicate in vitro in response to concanavalin A stimulation, nor did they produce interleukin-2 (IL-2) following stimulation. Furthermore this concentration of gliotoxin also causes complete fragmentation of genomic DNA in treated cells, yet these cells are still capable of transferring clinical EAE. These data suggest that replication of donor lymphocytes in the recipient is not essential for the development of EAE.
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PMID:Replication of donor lymphocytes in recipients is not essential for the passive transfer of allergic encephalomyelitis. 245 57

T cell lines to myelin basic protein (MBP) developed following in vitro culture cause experimental allergic encephalomyelitis (EAE) upon transfer into naive recipient mice. We have, however, repeatedly observed that MBP-specific T cell lines lose their ability to transfer EAE after 40 days in culture. Analyses of such cell lines failed to show any differences in their proliferative responses to antigen, or in the secretion of interleukin-2 (IL-2) and/or IL-4 when compared to their encephalitogenic counterparts. In contrast, examinations of T cell receptor (TCR) beta-chain gene rearrangement patterns showed sequential changes in the clonal population of cells concomitant with the loss of encephalitogenic function. Furthermore, transfer of a non-encephalitogenic, genotypically altered cell line after long-term in vitro culture into mice challenged with MBP suppressed the development of EAE. These findings suggest that the development of such putative regulatory cells in vivo may be involved in the recovery in EAE.
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PMID:Spontaneous development in vitro of a myelin basic protein-specific suppressor T cell line. 247 59


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