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)

PVG/c rats, infected 3 days previously with 10(3) Trypanosoma brucei brucei S.42 organisms failed to develop adjuvant disease in response to an intradermal inoculation of mycobacterial adjuvant. By contrast, similarly infected rats, immunized with heterologous brain and spinal cord in Freund's complete adjuvant with pertussis vaccine as a secondary adjuvant, developed clinical signs of allergic encephalomyelitis (EAE) at least as severe as those in uninfected rats. Delayed hypersensitivity reactions to PPD were depressed in trypanosome-infected, adjuvant-injected rats, as were the reactions to myelin basic protein in infected rats developing EAE. There appeared to be no cross-reactivity between trypanosomal antigen and myelin basic protein which could account for the lack of suppression of EAE. It is suggested that the different extent to which autoimmunity is involved in these two experimental allergic diseases may account for the differential suppressive activity of trypanosome infections upon them.
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PMID:Differential suppression of experimental allergic diseases in rats infected with trypanosomes. 9 15

We examined the effect of acute immunosuppression with high dose cyclophosphamide (CY), followed by syngeneic T-cell-depleted bone marrow transplantation (SBMT) on chronic-relapsing autoimmune encephalomyelitis (CR-EAE) induced in SJL/J mice by immunization with mouse spinal cord homogenate (MSCH) in adjuvant. Treatment of mice on day 9 post immunization, before the appearance of clinical signs of the disease, delayed the onset of paralysis, but did not affect its clinical course. Treatment on day 2-3 after the first clinical signs led to complete regression of the disease. During a period of 3 months, only one of the 15 mice treated after the the onset of CR-EAE relapsed, as compared to a total of 21 relapses in the 15 untreated animals. A rechallenge with MSCH in adjuvant on day 78 after immunization induced a severe relapse in all untreated mice, with 78% mortality; in contrast, only 25% of mice treated with CY and SBMT relapsed when similarly rechallenged. Lymphocytes from mice treated with CY and SBMT showed reduced in vitro proliferative responses to myelin basic protein (GMBP) and PPD, even after the rechallenge with MSCH. Our results show that high dose CY for elimination of immunocompetent lymphocytes, followed by SBMT rescue, suppresses CR-EAE and induces tolerance to the immunizing antigens. These results may encourage attempts to apply a similar therapeutic principle in life-threatening human neurological autoimmune diseases.
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PMID:Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): treatment and induction of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation. 164 96

Activation of antigen-specific T lymphocyte lines requires presentation of the relevant antigen by syngeneic accessory cells (AC) that express Class II MHC gene products. To determine if the T cell activation signal was AC associated or was shed into the medium, supernatants from rat thymic AC populations pulsed with guinea pig basic protein (GP-BP) or PPD were used to stimulate resting BP- or PPD-reactive T cell lines derived from Lewis or BN rats. Cellfree supernatants were found to stimulate the T cell lines in an antigen-specific, strain-restricted manner, reflecting the pattern of stimulation observed with intact AC used. The activity of the cellfree supernatant could be enhanced five to 20 times in the presence of activated T lymphocytes, the optimal production occurring over a 6-hr period. The cellfree T lymphocyte activation signal produced in the presence of activated T cell products contained both an antigen-specific, MHC-restricted component (85%) and an antigen-independent, mitogenic component (15%). Supernatants containing GP-BP but not bovine BP or PPD induced highly significant proliferation of the Lewis rat-derived BP-1 T lymphocyte line, and transfer of these supernatant-activated cells produced clinical signs of experimental autoimmune encephalomyelitis (EAE) and DTH reactions to GP-BP. The GP-BP component was not inhibited by either of two monoclonal antibodies directed at determinants on either side of the epitope(s) recognized by BP-1 cells. However, stimulation was inhibited by an anti-I-A but not an anti-I-E monoclonal antibody, suggesting the involvement of a Class II MHC gene product on the T cell activation signal. The supernatant activity could be separated by ultracentrifugation at 100,000 X G for 4 hr into a microsomal pellet and an ultrasupernatant, and both fractions had greatly reduced activity on resting T cells until they were reconstituted by vigorous mixing. These results suggest that T effector cells can be activated by AC-derived microsomal fragments bearing Class II antigens that associate noncovalently with processed antigen. This cellfree signal is sufficient to activate encephalitogenic T lymphocytes to transfer clinical EAE and DTH reactions without need for a direct T cell-AC interaction.
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PMID:Activation of an encephalitogenic T lymphocyte line with a cellfree supernatant containing basic protein and I region gene products. 243 25

Experimental autoimmune encephalomyelitis (EAE) and/or tuberculin sensitivity were transferred to histocompatible recipients with myelin basic protein-stimulated and/or PPD stimulated guinea pig lymph node T cells previously separated by depletion of B cells ("panning") on rabbit anti-guinea pig Ig antibody-coated Petri plates. The depletion was augmented by complement-mediated lysis using mouse anti-guinea pig B-cell monoclonal antibody (31D2), rabbit anti-mouse Ig, and rabbit complement. B cells did not transfer EAE nor provide protection against active immunization with guinea pig spinal cord antigen.
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PMID:Transfer of autoimmune encephalomyelitis with T lymphocytes in strain 13 guinea pigs. 243 54

Oral administration of spirogermanium (Sg), inhibits the development of immune-mediated hindpaw inflammation in the rat model of adjuvant arthritis (AA) and DTH responses to PPD (30 mg/kg/day). A similar dosing protocol inhibits hindleg paralysis in experimental autoimmune encephalomyelitis (EAE). The spleens of these animals and those of normal rats contain radiation resistant (2000 R) non-specific suppressor cells (SC) which bear some similarity to those generated following total lymphoid irradiation (TLI). These cells do not appear to be mature T cells, they are partially adherent to plastic, sephadex G10 and nylon wool, insensitive to indomethacin and are enriched in a 1.07 g/ml fraction of a Percoll density gradient.
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PMID:Inhibition of autoimmune disease and the generation of suppressor cells by spirogermanium: a biological profile similar to total lymphoid irradiation. 252 42

A T lymphocyte line, BP-1, expressing the T helper phenotype was selected from Lewis rats immunized with guinea pig myelin basic protein (GP-BP) in complete Freund's adjuvant (CFA). The BP-1 line responded specifically to GP-BP but not to PPD after the first round of selection, and responded to rat but not human or bovine BP. When injected i.p. into histocompatible Lewis or F1 (Lewis X P2) recipients, the BP-1 line induced both clinical signs of experimental autoimmune encephalomyelitis (EAE) and delayed type hypersensitivity (DTH) reactions in ears challenged intradermally with GP-BP but not PPD. The severity of clinical signs and the degree of ear swelling were dependent on the dose of BP-1 cells injected. Both activities were detectable with as few as 0.1 X 10(6) BP-1 line cells and required prior activation of the line cells with GP-BP presented by accessory cells. Lewis rats that had recovered from EAE induced by injection of GP-BP in CFA were more susceptible than naive rats to BP-1 line-mediated disease, requiring as few as 0.03 X 10(6) line cells. Clinical EAE and DTH could be serially transferred into F1 (Lewis X P2) recipients with BP-1 cells and back to nonirradiated Lewis parents with activated splenocytes, suggesting that BP-1 cells persist in recipient rats. These results demonstrate the potent biologic activities of an autoreactive BP-specific T lymphocyte line. This line possesses properties similar to BP lines described previously as well as to culture-conditioned splenic T effector cells; thus, the data presented here bridge the gap between these two approaches for studying T effector lymphocyte functions.
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PMID:A myelin basic protein-specific T lymphocyte line that mediates experimental autoimmune encephalomyelitis. 258 32

This study was undertaken to test the hypothesis that preferential responder strain-specific Ia expression can be detected in delayed hypersensitivity (DH) skin reactions. Seven adult (strain 2 X strain 13)F1 and two strain 13 guinea pigs were sensitized with poly-L glutamic acid-lysine (GL), poly-L glutamic acid-tyrosine (GT), and bovine insulin in complete Freund's adjuvant, and were skin tested with GL, GT, PPD, bovine insulin, porcine insulin (which has the same B chain as bovine insulin), and saline. Strain 2 guinea pigs react with bovine insulin A chain, GL, and PPD but not with GT or the bovine insulin B chain, whereas strain 13 guinea pigs react with bovine insulin B chain, GT, and PPD but not with GL or bovine insulin A chain. The (2 X 13)F1 animals had positive DH responses to GT, GL, PPD, and bovine insulin. At 24 hr, areas of induration were measured and the test sites and draining lymph nodes were biopsied. Cryostat sections were stained with monoclonal antibodies to strain 2 Ia, strain 13 Ia, and Ia framework determinants with immunoperoxidase. Stained dermal and subdermal inflammatory cells and vessels were counted on coded slides. In GT tests, there was more staining of dermal and subdermal cells and vessels for strain 13 Ia than strain 2 Ia (p less than 0.02). In bovine insulin tests there was more staining of dermal cells and vessels for strain 13 than strain 2 Ia (p less than 0.05). In GL tests there was more staining on dermal vessels and subdermal cells and vessels of strain 2 Ia than strain 13 Ia (p less than 0.05). There was much greater staining of strain 2 Ia of dermal cells and vessels in GL tests compared with strain 2 Ia staining in GT and bovine insulin tests (p less than 0.02, cells; p less than 0.01, vessels). No significant differences between strain 2 and strain 13 Ia expression were found in PPD, porcine insulin tests, saline controls, or in lymph nodes that drained sensitization sites from animals in which GL and GT had been injected on different sides. Anti-Ia framework expression generally correlated with the greater parental strain Ia in each reaction. These findings and previous observations in experimental allergic encephalomyelitis suggest that responder type Ia may be selectively found in vivo on mononuclear and endothelial cells in sites of T cell-mediated hypersensitivity reactions.
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PMID:Responder strain-specific enhancement of endothelial and mononuclear cell Ia in delayed hypersensitivity reactions in (strain 2 X strain 13)F1 guinea pigs. 353 27

Copolymer-1 (Cop-1) inhibits the T cell response to myelin basic protein (MBP), suppresses experimental autoimmune encephalomyelitis in many animal species, and was recently shown to be effective in the treatment of multiple sclerosis (MS). Interferon beta-1b (IFN-beta), an immune modulator with no antigenic specificity, is already approved for treatment of relapsing-remitting MS. We investigated the combined effect of these two agents on the cellular immune response to MBP. Antigen-specific Th1-like cell lines were generated from two healthy individuals with different MHC phenotypes. Cop-1 inhibited the proliferation of all MBP-specific lines but had no suppressive effect on tuberculin (PPD) or tetanus toxoid (TT)-specific T cell lines from either donor, while IFN-beta non-specifically reduced proliferation of all T cell lines. When combined in vitro, Cop-1 and IFN-beta had additive suppressive effects on proliferation of MBP-specific T cell lines, with 70-100% inhibition depending on the concentration of antigen. Synthesis of the pro-inflammatory cytokines interleukin-2 and IFN-gamma by MBP-specific lines was also inhibited additively (up to 100%). When antigen-presenting cells (APC) were pretreated with Cop-1, IFN-beta or both, T cell proliferation was inhibited in the same additive pattern, even though the inhibitors were not present in culture, indicating that they acted primarily through modulation of APC function. Additive effects were not found with PPD- or TT-specific cell lines. Pretreatment of APC with IFN-beta resulted in dose-dependent reduction in HLA-DR and HLA-DQ expression, which paralleled inhibition of T cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Additive effects of copolymer-1 and interferon beta-1b on the immune response to myelin basic protein. 759 54

Traditionally, statistical analyses of multiple limiting dilution analyses have used linear regression in comparing the fit of each analysis to a single-hit Poisson model. Multiple analyses can, however, result in an inflated type I error leading to spurious rejection of the null hypothesis. Logistic regression was used as an umbrella statistic to analyze eight limiting dilution analyses for antigen-reactive T cells from two mouse strains (SJL/J; B10.S), at two priming doses of antigen, for each of two antigens (porcine myelin basic protein, PMBP; purified protein derivative of M. tuberculosis, PPD) used to induce experimental allergic encephalomyelitis (EAE). This proved superior to traditional methods: six of the eight strain/dose/antigen combinations were consistent with a viable model, whereas only three of eight were consistent with the Poisson single-hit model. Moreover, only three of the resultant 32 standardized residual values (four per group times eight groups) fell outside the 95% confidence interval. Logistic regression, therefore, is recommended when nominal dependent measures can be structured as a function of more than one independent variable.
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PMID:Use of logistic regression in comparing multiple limiting dilution analyses of antigen-reactive T cells. 768 Mar 68

We investigated the mode of action of a new quinoline derivative, TAK-603 (ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmeth yl) quinoline-3-carboxylate), in adjuvant arthritis (AA), a model of rheumatoid arthritis. AA rat splenocytes transferred the arthritis to normal syngeneic rats upon inoculation, but the cells from AA rats treated with TAK-603 (6.25 mg/kg/day) caused only mild arthritis with significantly less foot pad swelling and a lower arthritis score. An effect of TAK-603 in the induction phase of AA was suggested. TAK-603 had little effect on CD4+ and CD8+ T-cell populations in the AA rat splenocytes. We therefore estimated the frequency of T-cells which are reactive to the so-called disease causative antigen using a limiting dilution assay (LDA). The ratio of T-cells responsive to PPD, which increased in AA rat splenocytes with the severity of the arthritis, was reduced in AA rats treated with TAK-603. Furthermore, the ratio of MBP (myelin basic protein)-reactive T-cells, which were generated in experimental allergic encephalomyelitis (EAE) rats, were also reduced by TAK-603 administration. These data suggest that TAK-603 acts on the immune system and reduces the number of cells reactive to the relevant antigen.
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PMID:Reduction of disease causative T-cells in experimental autoimmune disease models by a new antirheumatic drug, TAK-603. 940 35


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