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)

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

Mast cells (MC) have been implicated in the pathogenesis of experimental allergic encephalomyelitis (EAE). In order to further evaluate their role, several morphological and functional studies were performed. Semiquantitative counts of histological sections showed a significant reduction in MC numbers in EAE brains. In addition, a higher proportion of EAE MC (about 50-70%) appeared degranulated compared with about 20% degranulation in controls. Central nervous system (CNS) MC exhibited staining properties of connective tissue MC and about 98% of them, both in diseased and control rats, were located in the thalamus. They were not present in the spinal cord and did not relate to EAE lesions. In vitro incubation of peritoneal MC (of connective tissue phenotype) with either MBP, or with neuropeptides such as substance P or bradykinin resulted in release of beta-hexosaminidase and histamine. The latter responses were similar in both EAE and control rats. It is suggested that the decrease in number and in granular content of CNS MC in EAE may reflect prior in vivo activation. The fact that MC were activated by MBP and by neuropeptides in vitro suggests a possible mechanism of MC activation in EAE.
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PMID:Mast cells in experimental allergic encephalomyelitis: characterization, distribution in the CNS and in vitro activation by myelin basic protein and neuropeptides. 751 40

Interferon-gamma (IFN-gamma) is a cytokine with multiple activities on a variety of cells. Under various circumstances, IFN-gamma can exhibit either pro-inflammatory or inhibitory actions. Treatment of SJL/J mice with a monoclonal antibody (Mab) to IFN-gamma during the afferent limb of the immune response to myelin protein produced an enhancement of acute experimental allergic encephalomyelitis (EAE), with increased morbidity, mortality and earlier onset of disease. Systemic administration of IFN-gamma did not improve or worsen clinical outcome, but delayed disease onset. Passive transfer of immune lymph node cells co-activated with MBP and anti-IFN-gamma Mab resulted in more sever disease than that induced by MBP stimulated cells or MBP and IFN-gamma co-stimulated cells. However, in vitro proliferation of an MBP specific T cell line was not influenced by IFN-gamma nor anti-IFN-gamma treatment. Mab to IFN-gamma inhibited suppressor function, in a non-specific assay. These in vivo and in vitro results suggest that systemic IFN-gamma serves as a physiological regulator of a suppressor mechanism in EAE. The abrogation of this regulatory mechanism by anti-IFN-gamma administration contributes to a more severe form of experimental allergic encephalomyelitis.
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PMID:Monoclonal anti-gamma interferon antibodies enhance experimental allergic encephalomyelitis. 751 6

We have previously shown the presence of suppressor cells in Lewis rats at the time of spontaneous recovery from experimental autoimmune encephalomyelitis (EAE). These cells, called 'recovery-associated suppressor cells' (RASC), are capable of preventing active EAE and inhibiting in vitro the specific proliferative response of encephalitogenic anti-MBP T cell line cells. The present investigations were undertaken in order to lend support to the hypothesis that RASC play an active role in the recovery. We found that RASC can prevent adoptive EAE when admixed with already activated, but not resting, anti-MBP T cells or when injected into the recipients separately from the encephalitogenic cells. They can also arrest the course of an ongoing disease when injected after the beginning of the clinical signs. This study provides the first direct demonstration of the downregulation of an ongoing EAE by suppressor cells.
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PMID:Regulation of experimental autoimmune encephalomyelitis: inhibition of adoptive experimental autoimmune encephalomyelitis by 'recovery-associated suppressor cells'. 752 Sep 17

The authors present a brief historical sketch of the development of our understanding of immune responses to myelin proteolipid protein (PLP) and the acceptance of PLP as a potent antigen in the induction of experimental allergic encephalomyelitis (EAE). The distinct characteristics of the PLP molecule that may contribute to complex immune responses to this protein are reviewed and these responses are compared with those to MBP, both in the pathology of EAE and at the level of the T cell. Recent evidence demonstrating differences between T cell responses to PLP and MBP is reviewed. Finally, the potential contribution of immune responses to PLP in human diseases, particularly multiple sclerosis (MS), that have been identified to date are then summarized.
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PMID:Minireview: autoimmune responses to myelin proteolipid protein. 752 54

Chronic relapsing experimental allergic encephalomyelitis (CR.EAE) was induced by immunizing Lewis rats with total guinea-pig spinal cord (GPSC) tissue emulsified in enriched complete Freund's adjuvant (CFA). The proliferative responses of draining inguinal and popliteal lymph node cells to GP.MBP, purified protein derivative (PPD) and concanavalin A (ConA) appeared significantly modulated according to the clinical state of the animals. Responses appeared significantly decreased in both lymphoid compartments during the recovery periods compared with that during relapses. Therapeutic treatment of CR.EAE with cyclosporin and different lysolecithin derivatives, such as ET-18-OCH3, SRI 62-843 and MLS 266-337, starting at the spontaneous remission of the first disease bout, could suppress the manifestation of further relapses. Whereas cyclosporin only delayed the onset of the disease relapse until discontinuation of treatment, all lysolecithins showed a curative effect in most animals. Plasma corticosterone levels measured at different time points in placebo, cyclosporin and MLS 266-377-treated rats showed a strong correlation with the clinical state of the animals. High corticosterone levels were detected during stages of acute paralysis, whereas a decrease to normal levels was noted during each recovery phase.
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PMID:Immunoregulation and drug treatment in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. 754 48

Experimental autoimmune encephalomyelitis was induced in SJL/J mice by adoptive transfer of a MBP exon-2 peptide-specific T cell line. The T cell line, when tested for antigen specificity, reacted strongly with exon-2 peptide, but not with MBP peptides pAc1-11, p43-88, p89-101 or PLP p139-151. The specificity of splenic or lymph node T cells isolated from mice with acute or first relapse EAE induced by adoptive transfer of the exon-2-specific T cell line was identical to the transferred line. Splenocytes or lymphocytes isolated from mice at the second relapse were reactive with MBP p43-88, p89-101 and PLP p139-151 in addition to exon-2 peptide and MBP peptide Ac1-11. T cell lines selected by culture with MBP exon-2 peptide or PLP p139-151 from splenic cells from mice with relapsing EAE were weakly encephalitogenic; however, T cell lines selected from the same mice with MBP pAc1-11 were not encephalitogenic. T cells from the exon-2 and p139-151 T cell lines primed recipients for rapid onset severe EAE, whereas the pAc1-11 T cell line did not. T cells from the exon-2-specific line did not express V beta 17a+ TCR; however, peptide-specific T cell lines derived from the spleens of relapsing animals did express this TCR gene segment providing direct evidence of recruitment and sensitization of recipient T cells.
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PMID:The immune response to a subdominant epitope in myelin basic protein exon-2 results in immunity to intra- and intermolecular dominant epitopes. 759 53

The potential role of certain important immunoregulatory and effector cytokines in autoimmune neuroinflammation have been studied. We have examined the expression of mRNA, with in situ hybridization, of interferon gamma (IFN-gamma), interleukin 4 (IL-4) and transforming growth factor beta (TGF-beta) both in sections of spinal cords and the antigen-induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63-88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords, the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4. Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63-88 induced lymphoid cells to TGF-beta production. Thus, an autoantigen-specific production of TGF-beta occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive autoimmunity systemically.
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PMID:Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells. 760 12

Encephalitogenic T cells not only cause experimental autoimmune encephalomyelitis (EAE), but they induce resistance against subsequent induction of the disease as well. The T cell receptor (TcR) of encephalitogenic T cells is believed to contribute to their vaccinating activity. Findings in support of this assumption include the apparent restricted use of particular TcR elements, such as V beta 8.2. However, results from other laboratories including ours do not support this idea. We previously showed that rat T cells reactive against the conserved encephalitogenic epitope of myelin basic protein [MBP (87-99)] use the TcR in a heterogeneous fashion (Sun, D. et al., Eur. J. Immunol. 1992. 22: 591). Here we show, in Lewis rats, that the TcR beta chain usage of T cells specific for the dominant MBP (68-88) epitope is not restricted to V beta 8.2. Not only did such cells rely on diverse V beta chains, but some non-V beta 8-bearing cells were highly encephalitogenic. We also show that antigen-presenting cells (APC) play an important role in determining the TcR usage of MBP-specific T cells. Stimulation of MBP (68-88)-specific T cell lines by cloned APC derived from different sources resulted in selection of encephalitogenic T cells bearing different TcR beta chains.
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PMID:Diverse T cell receptor beta chain usage by rat encephalitogenic T cells reactive to residues 68-88 of myelin basic protein. 767 47

Using an inducible expression vector in Escherichia coli, we have expressed, purified, and biologically characterized recombinant human myelin basic protein (r-MBP). The recombinant protein binds in cation-exchange chromatography with similar affinity to purified, human MBP, and elutes as a single, 18.5-kDa species as judged by SDS-PAGE. The recombinant protein exhibits similar conformation to native MBP, as demonstrated by ELISA reactivity with a panel of six monoclonal antibodies directed against at least three different epitopes on human MBP. Additionally, recombinant MBP can trigger the proliferation of human T cell clones recognizing MBP, can induce experimental autoimmune encephalomyelitis (EAE) in the SJL mouse, and is capable of suppressing EAE following tolerization via oral administration. Most important, by using a novel method of purification, the recombinant protein preparation contains no detectable proteolytically derived fragments of MBP, a significant advantage over MBP purified from protease-rich central nervous system tissue. Purified recombinant MBP produced in E. coli will be useful as a biological reagent where highly purified protein devoid of degradation products is needed. Relevance to the study of antigen processing, interactions between MHC and the TCR, as well as for the investigation of antigen-driven immune tolerance are discussed.
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PMID:Biological activity of recombinant human myelin basic protein. 768 37


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