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)

Purified lipophilin, a hydrophobic lipoprotein of myelin, induces a cell-mediated demyelinating disease of the central nervous system similar to experimental allergic encephalomyelitis (EAE) induced by the myelin basic protein (MBP). Guinea pigs challenged with lipophilin (emulsified with CFA) developed clinical and histological signs of disease indistinguishable from those developed by animals similarly challenged with MBP. Both lipophilin and MBP induced and elicited delayed-type hypersensitivity in animals challenged with respective antigens. Tryptophan, an essential component of the MBP-determinant for disease in guinea pigs, is required for the encephalitogenicity of lipophilin.
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PMID:Myelin lipophilin-induced demyelinating disease of the central nervous system. 746 81

We have been studying the suppression of experimental autoimmune encephalomyelitis in the Lewis rat after oral administration of myelin basic protein (MBP). Suppression is mediated by CD8+ T cells that adoptively transfer protection and suppress immune responses in vitro. This suppression is mediated by secretion of TGF-beta following triggering by the fed antigen. In the present study, we tested the ability of overlapping 20 amino acid peptides from MBP to trigger suppression mediated by spleen cells from Lewis rats orally tolerized to MBP. Using a transwell system, we found that spleen cells from MBP orally tolerized animals stimulated by residues 21-40, 51-70 and 101-120 of MBP suppress proliferative responses of an ovalbumin specific cell line. This suppression correlated with secretion of TGF-beta by cells stimulated with the peptide. In addition, T cells from animals fed the tolerogenic peptide 21-40 alone secreted TGF-beta whereas no TGF-beta release or in vitro suppression was observed in animals fed the MBP encephalitogenic determinant 71-90. The 71-90 peptide triggered proliferation of MBP primed cells from animals immunized with MBP/CFA whereas the suppressor epitopes identified above did not. Furthermore, oral administration of peptide 21-40 suppressed disease induced by peptide 71-90. DTH responses to 71-90 were not affected by oral administration of peptide 21-40 whereas DTH responses to whole MBP were suppressed. These results demonstrate that distinct suppressor determinants exist on MBP which are separate from encephalitogenic determinants, and that epitope-driven bystander suppression plays an important role in down-regulation of tissue specific autoimmune processes following oral tolerization. These findings have important implications for the design of tissue specific targeted immunotherapy by oral tolerization in humans.
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PMID:Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression. 750 26

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

Uveitis of unknown etiology is known to occur in association with various systemic disorders. We now report that anterior uveitis (AU) can be produced by T cell immunity to myelin basic protein (BP) and accompanies experimental autoimmune encephalomyelitis (EAE). EAE with AU was induced in Lewis rats by immunization to BP in CFA or by immunization to various BP peptides including the encephalitogenic 71-90 peptide. Slit-lamp biomicroscopy of BP-immunized Lewis rats revealed AU, characterised by inflammation of the iris, in 73% of the eyes. The onset of AU in actively immunized rats varied between days 12 and 26, often appearing after spontaneous remission of the paralysis, the hallmark of EAE. The course of AU was progressive, affecting more than 50% of the surface of the iris in 16 of 29 diseased eyes. Like the paralysis, the AU was self-limiting: within 2 weeks the disease remitted. In addition, AU could be adoptively transferred to naive and irradiated rats by a T cell clone specific for BP peptide 71-90. The present observations are compatible with the idea that AU may be triggered by BP-reactive T cells. The myelinated nerves present in the iris have been shown to contain BP. However, these peripheral nerves would now appear to be the only peripheral nerves susceptible to acute EAE.
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PMID:T cell immunity to myelin basic protein induces anterior uveitis in Lewis rats. 751 33

We have used adoptive transfer of myelin basic protein (MBP)-reactive lymphocytes in the Lewis rat model of experimental allergic encephalomyelitis (EAE) to identify stages of effector cell development and to investigate the nature of the subsequent recipient response to the transferred cells. Depending on the timing of cell collection, lymph node cells (LNC) obtained from MBP-CFA (MBP emulsified in complete Freund's adjuvant)-immunized donors may directly transfer clinical disease; however, independent of disease development, recipients of LNC develop early onset of clinical disease following immunization of the recipients with MBP-CFA, consistent with the presence of MBP-memory cells in the LNC transfer inoculum. Similarly obtained spleen cells do not directly transfer disease and do not contain MBP-memory cells (as defined by the early onset of clinical disease following MBP-CFA challenge). Spleen cells adoptively transfer clinical disease only following in vitro culture stimulation with antigen or selected mitogens. Recipients of the primary culture-derived encephalitogenic spleen cells also develop an accelerated onset of clinical disease following MBP-CFA challenge, indicative of the presence of MBP-memory cells, and are not vaccinated. Encephalitogenic T cell lines adoptively transfer clinical disease, and in most cases recipients are vaccinated to MBP-CFA-induced active disease, but remain susceptible to adoptively transferred disease. Co-transfer of encephalitogenic T cell line cells with MBP-reactive lymph node or encephalitogenic spleen cells does not alter the vaccination response. We have found that during the process of T cell line development, the vaccinating phenotype is acquired following the second antigen stimulation cycle. These studies also demonstrate that regulation induced by T cell vaccination blocks the development of effector cells from precursor cells and that such regulation is also equally effective in blocking disease development in recipients which have increased numbers of memory cells. Thus, the response to T cell vaccination, once established, is fully capable of inhibiting the development of effector cells from increased numbers of precursor/memory cells, a response that would be needed in the clinical application of vaccination-induced resistance.
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PMID:Adoptive transfer of experimental allergic encephalomyelitis: recipient response to myelin basic protein-reactive lymphocytes. 752 47

To explore the mechanisms responsible for the development of tolerance to allografts after intrathymic (IT) injection of alloantigen, the well-defined model of experimental autoimmune encephalomyelitis (EAE), which mimics the human autoimmune disease multiple sclerosis, was used. This inflammatory neurologic syndrome is initiated by myelin basic protein (MBP)-reactive CD4+ T lymphocytes restricted to self-MHC class II molecules. Naive adult, EAE-susceptible Lewis (RT1(1) rats were treated IT, i.v., or i.p. with a single dose (100 micrograms) of guinea pig-myelin basic protein (GP-MBP 1-176) in PBS plus 1 ml rabbit anti-rat lymphocyte serum i.p. Twenty-one days later, all rats were challenged by intradermal hind footpad injections of 50 micrograms GP-MBP in PBS emulsified in CFA. Only IT, but not i.p. or i.v., administration of GP-MBP plus anti-lymphocyte serum conferred marked resistance to a subsequent systemic challenge of GP-MBP, as demonstrated by the prevention of weight loss and paralysis characteristic of EAE. The IT administration dramatically decreased the size and number of histologic perivascular infiltrates observed per visual field in spinal cord of the tolerant animals and decreased GP-MBP-specific T lymphocyte in vitro proliferation (p < 0.01), whereas proliferation to a nonspecific mitogen (Con A) was not altered. With the addition of rIL-2, the decreased Ag-specific proliferative responses of IT-treated animals increased to control levels. Adoptive transfer of 100 x 10(6) splenocytes from tolerant hosts i.v. to naive syngeneic Lewis rats challenge with 100 micrograms GP-MBP in CFA had no effect on clinical or histologic EAE. Exposure of MBP to maturing thymocytes results in functionally immunounresponsive lymphocytes and prevention of autoimmune EAE.
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PMID:Immunological tolerance to a defined myelin basic protein antigen administered intrathymically. 752 8

Chronic/relapsing experimental allergic encephalomyelitis (CREAE) serves as an animal model for relapsing/remitting multiple sclerosis. Treatment with the beta-adrenergic agonist isoproterenol or the beta 2-adrenergic agonist terbutaline significantly suppressed both the first acute attack and the number of relapses in CREAE Lewis rats. The number of relapses was decreased even when treatment with beta-adrenergic agonist was started after the onset of the first acute attack of CREAE. beta-adrenergic receptor number was increased significantly on splenocytes from CREAE rats as compared to healthy controls or CFA-injected rats. Terbutaline treatment of CREAE rats lowered the splenocyte receptor number to normal values.
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PMID:Beta-adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats. 786 Jul 15

During experimental allergic encephalomyelitis (EAE), both blood-borne macrophages as well as activated, resident microglial cells are considered to be involved in inflammatory reactions in the central nervous system (CNS), resulting in the neurological deficits common to EAE. Both cell types can produce multiple mediators of tissue damage, among which are the reactive oxygen species (ROS). In this study we show that macrophages and microglial cells, isolated from the CNS of Lewis rats with clinical signs of EAE, exhibited significantly elevated spontaneous and phorbol myristate acetate (PMA)-inducible levels of ROS compared to similar cells isolated from healthy controls, sham (complete Freund's adjuvant, CFA)-immunized rats as well as rats sacrificed before the manifestation of clinical signs of EAE. However, during clinical EAE, peripheral blood mononuclear cells (PBMC) did not show increased spontaneous nor PMA-inducible ROS production compared to controls. In vivo treatment of EAE with catalase, which scavenges the ROS H2O2, markedly suppressed the severity of the disease as compared to sham (albumin)-treated controls. In contrast, superoxide dismutase had no effect on clinical signs. Our studies point at a putative functional role for ROS, and in particular H2O2, in the pathogenesis of EAE.
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PMID:Reactive oxygen species are involved in the pathogenesis of experimental allergic encephalomyelitis in Lewis rats. 786 Jul 16

Although T cell receptor (TCR) peptide therapy was initially reported to be a very effective method for prevention of the development of experimental autoimmune encephalomyelitis (EAE), it was recently demonstrated that the same peptide immunization led to enhanced and chronic EAE in some cases. In the present study, we examined the effect of the TCR peptide (V beta 8.2-39-59) vaccination on the development of EAE by employing several immunization protocols. We found that TCR peptide vaccination effectively prevented EAE development only when the peptide was injected with Mycobacterium tuberculosis-enriched CFA in the vicinity of the challenge site. Under such conditions, a sufficient number of peptide-reactive T cells were generated. Flow cytometry and immunohistochemical analyses using anti-peptide antibody and anti-V beta 8.2 mAb revealed that despite the presence of V beta 8.2+ cells, very few peptide-positive T cells appeared in the lymphoid organs throughout the course of EAE. These findings imply that antibodies that are generated after immunization with V beta 8P are hardly accessible to their specific epitopes in the native protein. Insufficient generation of both T cells and antibodies against V beta 8.2-positive T cells may be attributable to the outcome of the therapy. To establish effective TCR peptide immunotherapy, these disadvantages should be overcome by using other TCR sequences and/or by employing a more suitable adjuvant.
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PMID:T cell receptor peptide therapy for autoimmune encephalomyelitis: stronger immunization is necessary for effective vaccination. 811 76

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced by the adoptive transfer of CD4, myelin basic protein (MBP)-specific T cells. Superantigens activate T cells expressing appropriate TCR V genes. In this study, MBP-specific T cells activated in vitro with a superantigen, staphylococcal enterotoxin B (SEB), could adoptively transfer a severe form of EAE in (PLxSJL)F1 mice, but did not transfer disease in PL/J or SJL/J mice. SEB treatment of donor mice anergized MBP-specific T cells using V beta 8 in (PLxSJL)F1 mice, because subsequent in vitro activation with SEB resulted in a marked decrease in proliferation to SEB and inability to transfer EAE. However, donor cells from (PLxSJL)F1 mice immunized with MBP/CFA that had been exposed to SEB in vivo before MBP stimulation in vitro still produced EAE in recipient mice. To confirm that non-V beta 8 T cells could transfer disease, donor mice were treated with antibody that eliminated V beta 8 T cells; MBP-activated T cells from these mice could still transfer EAE. Finally, EAE induced by SEB-activated T cells was substantially reduced in mice receiving anti-V beta 8 therapy in vivo. The ability of superantigens to activate encephalitogenic T cells may have relevance to human diseases such as multiple sclerosis.
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PMID:Superantigen modulation of experimental allergic encephalomyelitis: activation of anergy determines outcome. 812 Apr 6


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