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) can be transferred by spleen cells stimulated in vitro with D-mannose-binding lectins but not with N-acetyl-D-galactosamine (GalNAc)-binding lectins. EAE could also be passively transferred by spleen cells following incubation with wheat germ agglutinin (WGA), in which case the disease transfer was abolished by the specific hapten inhibitor, N-acetyl-D-glucosamine. In the presence of rat T cell monoclonal antibody, either W3/25 or OX-8, both concanavalin A and Wisteria floribunda agglutinin stimulated helper and suppressor T subpopulations. On the other hand, GalNAc-binding lectins were less effective than D-mannose-binding lectins in generating interleukin 2 (IL2) in the culture supernatant, whereas WGA-stimulated spleen cells did not produce IL2. Furthermore, spleen cells cultured with pure IL2 could not transfer EAE to the recipients. These data suggest that some factors distinct from IL2 are required for the differentiation of EAE-effector precursors into the final effector cells in this transfer system.
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PMID:Adoptive transfer of experimental allergic encephalomyelitis with lectin-activated spleen cells. Part 2. Studies on T cell subsets and interleukin 2 production. 348 46

The in vitro and in vivo effects of the experimental immunomodulatory agent Wy-18,251 (3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid) were studied in comparison with levamisole and indomethacin. Levamisole (4 mg/kg, i.v.) but not Wy-18,251 (less than or equal to 10 mg/kg, i.v.) enhanced carbon clearance rates in vivo in mice. Both Wy-18,251 and levamisole (100 mg/kg, p.o.) significantly suppressed the symptoms of experimental allergic encephalomyelitis (EAE) in rats injected with spinal cord emulsion, but neither were as effective as tilorone in this model. Wy-18,251 and levamisole (1-100 mg/kg, p.o.) suppressed the in vivo generation of plaque-forming cells (PFC) in mice immunized with sheep red blood cells while indomethacin (9 mg/kg, p.o.) enhanced PFC formation. All 3 agents (10(-5) - 10(-6) M) enhanced the in vitro ovalbumin (OA)-specific and Con A- or PHA-induced proliferative response and Con A-stimulated interleukin 2 (IL-2) synthesis of rat spleen cells. Furthermore, in vivo treatment of rats with 1-10 mg/kg (p.o.) of Wy-18,251 and levamisole but not indomethacin increased the subsequent in vitro mitogen or antigen (OA) responsiveness of spleen cells. None of the drugs (10(-5) - 10(-7) M) influenced the natural killer cell (NK) activity of rat spleen cells when incorporated directly into the 51Cr release NK assay.
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PMID:Immunomodulatory activity of Wy-18,251 (3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid). 387 43

Although spleen cells (SpC) from Lewis rats that have been immunized with guinea pig myelin basic protein in complete Freund's adjuvant do not transfer experimental autoimmune encephalomyelitis (EAE) to syngeneic recipients, we report that effector cells of EAE can be activated in SpC suspensions during mixed lymphocyte reactions (MLR) to allogeneic SpC. Effector cell activation correlates with interleukin 2 (IL 2) production. The results are consistent with the hypothesis that autoreactive cells may be generated as a result of an immune response to exogenous antigens.
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PMID:Autoimmune effector cells. VI. Transfer of experimental allergic encephalomyelitis with spleen cells activated in mixed lymphocyte cultures. 623 61

This study was conducted to further characterize the effector cells of experimental allergic encephalomyelitis (EAE) which are activated in vitro when spleen cells from Lewis rats previously immunized with myelin basic protein and adjuvant are cultured with antigen prior to transfer to syngeneic recipients. The effector cells were isolated on discontinuous Percoll gradients in the cell fraction that floated on Percoll with a buoyant density of 1.067 kg/l. These cells (designated fraction 1) transferred EAE and incorporated [3H]dThd in culture. Fraction 1 was enriched for T cells when evaluated with monoclonal anti-rat T cell serum W3/13 and deficient in Ig+ cells; approximately 33% were positive with monoclonal anti-rat T cell serum W3/25. In contrast, the small, nonproliferating cells found in higher density Percoll fractions did not transfer EAE. When fraction 1 was recultured in the presence of basic protein and interleukin 2 for 72 h, these cells retained the ability to transfer EAE. Moreover, these recultured cells exhibited an increase in the W3/25 antigen and a decrease in the W3/13 marker. It was concluded that a subset of T cells which bear the W3/25 marker is involved in the transfer of EAE.
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PMID:Autoimmune effector cells. II. Transfer of experimental allergic encephalomyelitis with a subset of T lymphocytes. 698 Jan 30

Cloned CD4 T cell lines that recognize the Ac1-16 peptide of myelin basic protein bound to I-Au were isolated and used to analyze the immunopathogenesis of experimental autoimmune encephalomyelitis (EAE). T helper type 1 (Th1) clones induced disease, while Th2 clones did not. Using variants of a single cloned Th1 line, the surface expression of alpha 4 integrins (very late antigen 4 [VLA-4]) was identified as a major pathogenic factor. Encephalitogenic clones and nonencephalitogenic variants differ by 10-fold in their level of surface expression of alpha 4 integrin and in their ability to bind to endothelial cells and recombinant vascular cell adhesion molecule 1 (VCAM-1). The alpha 4 integrin-high, disease-inducing cloned Th1 T cells enter brain parenchyma in abundance, while alpha 4 integrin-low, nonencephalitogenic Th1 cells do not. Moreover, antibodies to alpha 4 integrin, its ligand VCAM-1, and intercellular adhesion molecule 1 all influence the pathogenicity of this encephalitogenic clone in vivo. The importance of the expression of VLA-4 for encephalitogenicity is not unique to cloned T cell lines, as similar results were obtained using myelin basic protein-primed lymph node T cells. alpha 4 integrin levels did not affect antigen responsiveness or production of the Th1 cytokines interleukin 2, interferon gamma, and lymphotoxin/tumor necrosis factor beta; and antibodies against alpha 4 integrin did not block antigen recognition in vitro. Thus, we conclude that surface expression of alpha 4 integrin is important in CD4 T cell entry into brain parenchyma. A general conclusion of these studies is that alpha 4 integrins may be crucial in allowing activated effector T cells to leave blood and enter the brain and other tissues to clear infections.
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PMID:Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. 767 16

Brown-Norway (BN) rats injected with HgCl2 develop a systemic autoimmune disease associated with a polyclonal B cell activation, due to autoreactive T cells specific for self-class II molecules, while Lewis (LEW) rats injected with HgCl2 do not exhibit autoimmunity and develop a non-antigen-specific, CD8-mediated immunosuppression assessed by a depression of T cell functions, and a protection against experimental autoimmune encephalomyelitis (EAE). Resistance to HgCl2-induced autoimmunity is not due to these suppressor cells since treatment with an anti-CD8 monoclonal antibody (mAb) did not allow autoimmunity to appear. The absence of autoimmunity in this strain could result from the absence of autoreactive T cells, or from quantitative or qualitative differences of these cells between susceptible and resistant strains. In the present study, we show that CD4+ anti-class II T cells are present in HgCl2-injected LEW rats and are as frequent as in BN rats when assessed by limiting dilution analysis. LEW CD4+ autoreactive T cell lines were derived. They proliferated in the presence of normal class II-bearing cells, secreted interleukin 2, and did not induce B cells to produce immunoglobulins. Transfer of one of these lines, LEW Hg A, into normal LEW rats led to the appearance of CD8+ cells responsible for a non-antigen-specific immunosuppression that induced complete protection from EAE. Immunosuppression was abrogated after treatment with an anti-CD8 mAb. In vitro, CD8+ cells from rats injected with the LEW Hg A T cell line proliferated in the presence of activated T cells whatever their origin. We conclude that HgCl2 induces CD4+ autoreactive T cells that proliferate in the presence of class II+ cells in susceptible BN as well as in resistant LEW rats. But while these cells collaborate with B cells to produce autoantibodies in BN rats, they initiate in LEW rats a suppressor circuit involving antiergotypic CD8+ suppressor cells.
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PMID:Mercury-induced autoreactive anti-class II T cell line protects from experimental autoimmune encephalomyelitis by the bias of CD8+ antiergotypic cells in Lewis rats. 809 39

Orally administered antigens induce a state of immunologic hyporesponsiveness termed oral tolerance. Different mechanisms are involved in mediating oral tolerance depending on the dose fed. Low doses of antigen generate cytokine-secreting regulatory cells, whereas high doses induce anergy or deletion. We used mice transgenic for a T-cell receptor (TCR) derived from an encephalitogenic T-cell clone specific for the acetylated N-terminal peptide of myelin basic protein (MBP) Ac-1-11 plus I-Au to test whether a regulatory T cell could be generated from the same precursor cell as that of an encephalitogenic Th1 cell and whether the induction was dose dependent. The MBP TCR transgenic mice primarily have T cells of a precursor phenotype that produce interleukin 2 (IL-2) with little interferon gamma (IFN-gamma), IL-4, or transforming growth factor beta (TGF-beta). We fed transgenic animals a low-dose (1 mg x 5) or high-dose (25 mg x 1) regimen of mouse MBP and without further immunization spleen cells were tested for cytokine production. Low-dose feeding induced prominent secretion of IL-4, IL-10, and TGF-beta, whereas minimal secretion of these cytokines was observed with high-dose feeding. Little or no change was seen in proliferation or IL-2/IFN-gamma secretion in fed animals irrespective of the dose. To demonstrate in vivo functional activity of the cytokine-secreting cells generated by oral antigen, spleen cells from low-dose-fed animals were adoptively transferred into naive (PLJ x SJL)F1 mice that were then immunized for the development of experimental autoimmune encephalomyelitis (EAE). Marked suppression of EAE was observed when T cells were transferred from MBP-fed transgenic animals but not from animals that were not fed. In contrast to oral tolerization, s.c. immunization of transgenic animals with MBP in complete Freund's adjuvant induced IFN-gamma-secreting Th1 cells in vitro and experimental encephalomyelitis in vivo. Despite the large number of cells reactive to MBP in the transgenic animals, EAE was also suppressed by low-dose feeding of MBP prior to immunization. These results demonstrate that MBP-specific T cells can differentiate in vivo into encephalitogenic or regulatory T cells depending upon the context by which they are exposed to antigen.
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PMID:Oral tolerance in myelin basic protein T-cell receptor transgenic mice: suppression of autoimmune encephalomyelitis and dose-dependent induction of regulatory cells. 855 44

Oral administration of autoantigens can prevent and partially suppress autoimmune diseases in a number of experimental models, Depending on the dose of antigen fed, this approach appears to involve distinct yet reversible and short-lasting mechanisms (anergy/deletion and suppression) and usually requires repeated feeding of large (suppression) to massive (anergy/deletion) amounts of autoantigens to be effective. Most importantly, this approach is relatively less effective in animals already systemically sensitized to the fed antigen, such as in animals already harboring autoreactive T cells and, thus, presumably also in humans suffering from an autoimmune disorder. We have previously shown that feeding a single dose of minute amounts of antigens conjugated to cholera toxin B subunit (CTB) can effectively suppress delayed-type hypersensitivity reactions in systemically immune animals. We now report that feeding small amounts of myelin basic protein (MBP) conjugated to CTB either before or after disease induction protected rats from experimental autoimmune encephalomyelitis. Such treatment was as effective in suppressing interleukin 2 production and proliferative responses of lymph node cells to MBP as treatment involving repeated feeding with much larger (50- to 100-fold) doses of free MBP. Different from the latter treatment, which led to decreased production of interferon-gamma in lymph nodes, low-dose oral CTB-MBP treatment was associated with increased interferon-gamma production. Most importantly, low-dose oral CTB-MBP treatment greatly reduced the level of leukocyte infiltration into spinal cord tissue compared with treatment with repeated feeding of large doses of MBP. These results suggest that the protection from experimental autoimmune encephalomyelitis achieved by feeding CTB-conjugated myelin autoantigen involves immunomodulating mechanisms that are distinct from those implicated by conventional protocols of oral tolerance induction.
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PMID:Treatment of experimental autoimmune encephalomyelitis by feeding myelin basic protein conjugated to cholera toxin B subunit. 869 68

The Th1-like cytokines, interleukin 2 (IL-2), interferon gamma (IFN-gamma), and lymphotoxin alpha (LT-alpha) have been implicated in the immunopathogenesis of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), an animal model of immune mediated demyelination. These cytokines have been associated with opening of the blood brain barrier (BBB) in EAE and in vitro, but not in MS. We used an enzyme-linked immunospot (ELI-spot) assay to measure relative numbers of cytokine-secreting peripheral blood mononuclear cells (PBMC) from eight MS patients who were followed with serial monthly contrast-enhanced head magnetic resonance imagings (MRI) and phlebotomy. We found a significant positive correlation between changes in IL-2 secreting cells and MRI lesions over a 6-month time period. There was a weaker association between contrast-enhancing MRI lesions and IFN-gamma or LT-alpha secreting cells. These data are the first to show a significant positive correlation between any cytokine and serial gadolinium (Gd-) MRI disease activity in MS patients. The association between IFN-gamma and LT-alpha secretion and MRI lesions is less clear.
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PMID:ELI-spot of Th-1 cytokine secreting PBMC's in multiple sclerosis: correlation with MRI lesions. 963 Jan 70

During activation, T cells express receptors for receiving positive and negative costimulatory signals. Here we identify the B and T lymphocyte attenuator (BTLA), an immunoglobulin domain-containing glycoprotein with two immunoreceptor tyrosine-based inhibitory motifs. BTLA is not expressed by naive T cells, but it is induced during activation and remains expressed on T helper type 1 (T(H)1) but not T(H)2 cells. Crosslinking BTLA with antigen receptors induces its tyrosine phosphorylation and association with the Src homology domain 2 (SH2)-containing protein tyrosine phosphatases SHP-1 and SHP-2, and attenuates production of interleukin 2 (IL-2). BTLA-deficient T cells show increased proliferation, and BTLA-deficient mice have increased specific antibody responses and enhanced sensitivity to experimental autoimmune encephalomyelitis. B7x, a peripheral homolog of B7, is a ligand of BTLA. Thus, BTLA is a third inhibitory receptor on T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1).
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PMID:BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. 1283 Jan 42


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