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)

Immune suppression (immunoprotection) in experimental autoimmune encephalomyelitis (EAE) was studied in (SJL X BALB/c)F1 mice using inocular of mouse spinal cord homogenate (MSCH), or mouse basic protein of myelin (M-BPM), in Freund's incomplete adjuvant (FIA). Such immunization specifically recruited lymphoid cells which markedly suppressed the capacity of effector lymph node cells from appropriately immunized syngeneic mice to transfer adoptively EAE. Suppression was demonstrable with transfer of bone marrow and spleen cells, but not with lymph nodes or thymus cells. Adoptively transferred suppression was maximal when cells were injected 9-30 days after the suppressive injection. Inhibition of EAE by suppressor cells was specific for the relavant antigen BPM, and required viable cells. Treatment of cells with anti-Thy-1 serum before transfer abolished their suppressor activity. After adoptive transfer of suppressor cells into syngeneic recipients subsequently immunized for EAE, there was inhibition of EAE and reduced cell-mediated immune response to BPM as judged by macrophage migration inhibition assays. Hence, in mice at least, immuno-protection against EAE is explicable by recruitment of suppressor T lymphocytes with the dual capacities of inhibiting development of effector T cells after antigenic stimulation, and of blocking their damaging effects on the antigen in the central nervous system.
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PMID:Suppressor T cells prevent experimental autoimmune encephalomyelitis in mice. 30 68

Cellular transfer of experimental autoimmune encephalomyelitis (EAE) was effected in mice with lymph node and spleen cells from appropriately immunized donors. In contrast to lymphoid cells, immune serum did not transfer this autoimmune disease nor did serum have any facilitating or inhibitory effect on the capacity of lymphoid cells to transfer EAE. Transfer of EAE was effected in normal mice, lightly irradiated (350 rad) and lethally irradiated (850 rad) and bone marrow-protected mice, but not in mice which had been given 850 rad total-body irradiation. There was a striking augmentation of severity of transferred EAE in the lightly irradiated recipients, possibly attributable to selective radiosensitivity of suppressor T cells. Cell-mediated immunity but not circulating antibody to basic protein of myelin was demonstrated in recipients with transferred EAE. The immune lymphoid cells responsible for transfer of EAE were T lymphocytes. Thus transfer was successful after passage of sensitized cells through anti-immunoglobulin columns and was abrogated following treatment with anti-Thy-1 serum and complement. Neonatally thymectomized mice failed to develop either EAE, cell mediated immunity or humoral antibody against myelin basic protein (BPM). Inhibition of EAE and immune responsiveness was solely due to the removal of the source of thymus lymphocytes, because reconstitution of neonatally thymectomized mice with T lymphocytes completely restored these functions. It is concluded that T lymphocytes are required for the production and adoptive transfer of EAE, for the development of cell-mediated immunity to BPM and for the production of antibody to BPM.
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PMID:T cell necessity in the pathogenesis of experimental autoimmune encephalomyelitis in mice. 108 43

Using the patch-clamp technique in combination with fluorescence microscopy we have found an abnormality in voltage-gated K+ channel expression in T cells that represents the first molecular marker linking three disparate autoimmune diseases in mice. CD4-CD8-Thy-1.2+ (double-negative or DN) lymphocytes from every known murine model for systemic lupus erythematosus, type-1 diabetes mellitus and experimental allergic encephalomyelitis exhibit abnormally high numbers of an unusual K+ channel, termed type l compared to their phenotypic counterparts in normal mice. Other T cell subsets from these diseased mice retain their normal pattern of K+ channel expression. The unique K+ channel phenotype of DN T cells arises in parallel with the onset of autoimmunity. Although mitogen-activated T cells and rapidly proliferating thymocytes exhibit large numbers of K+ channels, these channels are of an electrophysiologically distinct type called n. Thus, abundant expression of type l K+ channels appears to be a useful marker for DN T cells associated with autoimmunity and may provide a valuable tool for delineating the role of DN T cells in the pathogenesis of autoimmune diseases.
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PMID:Autoimmune diseases linked to abnormal K+ channel expression in double-negative CD4-CD8- T cells. 197 90

Expression of voltage-gated K+ channels in mAb-defined T cell subsets from normal mice and mice with experimental autoimmune arthritis was studied with the patch-clamp whole-cell recording technique in combination with fluorescence microscopy. CD4+CD8- Th cells from DBA/1 LacJ mice with type II collagen arthritis expressed low levels of type n K+ channels, and CD4-CD8+ T cells (cytotoxic) showed small numbers of type l or n' K+ channels, like their phenotypic counterparts in normal mice. CD4-CD8-Thy-1.2+ (double negative or DN) T cells from the diseased mice, however, displayed an abundance of type l K+ channels compared to DN T cells in normal mice, or mice immunized with CFA. Furthermore, the aberrant expression of type l K+ channels correlated with the presence of active disease. DN T cells from mice with SLE, type-1 diabetes mellitus, and experimental allergic encephalomyelitis, also exhibited a high number of type l K+ channels. These results suggest that expression of numerous type l K+ channels may be a useful marker for DN T cells associated with these autoimmune disorders.
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PMID:CD4-CD8- T cells from mice with collagen arthritis display aberrant expression of type l K+ channels. 197 26

Mouse myelin basic protein (mBP)-specific T cell clones were generated from lines established from SJL/J mice immunized with mBP in complete Freund's adjuvant. These clones proliferated specifically to mBP and were propagated weekly with the same antigen for up to 8 mo. It is of particular interest that four of these phenotypic T helper clones were able to induce several T cell functions, including that of antibody production. These mBP-reactive T cell clones induced inflammatory infiltrations of the white matter of the central nervous system when transferred i.v. to irradiated (350 R) syngeneic naive recipients in concentrations as low as 0.5 X 10(6) cells/mouse. Lesions characteristic of experimental allergic encephalomyelitis (EAE) were observed as early as 5 days after transfer in the absence of clinical paralysis. Encephalitogenic clones, when added in vitro to a population of mBP-primed B cells in the presence of antigen, induced the production of anti-mBP antibodies determined by ELISA. In addition, the same clones, when transferred i.v., were found to mediate in vivo helper activity by inducing serum anti-mBP antibodies in the recipients. This response was delayed until 20 days after transfer and was abrogated by irradiation of the clones before injection. Finally, these mBP-specific specific clones were capable of mediating a specific delayed-type hypersensitivity (DTH) response. Although all four clones generated displayed the Thy-1.2+, L3T4+, Lyt-2- phenotype and proliferated specifically to mBP, only three were able to induce EAE, transfer DTH, and mediate helper activity.
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PMID:Passive transfer of experimental allergic encephalomyelitis by myelin basic protein-specific L3T4+ T cell clones possessing several functions. 243 15

Intracerebral inoculation of mice with Theiler's murine encephalomyelitis virus results in an intense inflammatory response of mononuclear leukocytes which infiltrate into the central nervous system. Resistant strains of mice have the ability to clear virus whereas susceptible strains become infected persistently and are associated with chronic demyelination which is proposed to be immune-mediated. In an attempt to better understand the role of the immune response during demyelination, mononuclear leukocytes were isolated from the central nervous system of infected mice and stained by an immunoperoxidase technique with anti-Thy-1.2, anti-L3T4, anti-Lyt-2 and anti-MAC-1 mAb. Infection of susceptible SJL/J mice resulted in a biphasic immune response which peaked on days 7 and 27 post-infection. In contrast, a single peak (day 7) was observed in resistant C57BL/10SNJ mice. The presence of Thy-1.2, L3T4, and MAC-1+ cells was similar between the two strains. However, although the number of Lyt-2+ cells peaked on day 7 in C57BL/10SNJ mice, they were not detected in SJL/J mice until 14 days post-infection and gradually increased in number over the course of infection. To further study the role of T cells in demyelination, serial frozen sections of brain and spinal cord were stained for the presence of Lyt-2 and L3T4+ cells in the lesions of chronically infected SJL/J mice. L3T4+ cells were observed predominantly in perivascular regions while Lyt-2+ cells were observed infiltrating the parenchyma. These results provide further evidence that Lyt-2+ lymphocytes are important in the mechanism of susceptibility/resistance to Theiler's murine encephalomyelitis virus-induced demyelination.
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PMID:Characterization of the inflammatory response in the central nervous system of mice susceptible or resistant to demyelination by Theiler's virus. 249 23

To investigate the sequence of immunopathologic events during lesion formation in acute experimental allergic encephalomyelitis (EAE), SJL/J mice were inoculated with isogeneic spinal cord in complete Freund's adjuvant (CFA) and with Bordetella pertussis on Days 1 and 3 postinoculation (PI). Mice were sampled at different time points PI and T cells, T-cell subsets. Ia+ cells, Ig+ cells, albumin, and Ig deposits were localized in frozen sections by the avidin-biotin complex (ABC) method and direct fluorescence. Furthermore, samples were stained for Ia antigen, myelin basic protein (MBP), and galactocerebroside (GC) localization on endothelial cells by the ABC technique. Clinical and pathologic observations were correlated with the immunopathologic results. It was found that early in the disease process myelin and Ia-antigens were demonstrable on endothelial cells within the central nervous system (CNS). Simultaneously, damage to the blood-brain barrier was apparent, as indicated by albumin deposits, and small numbers of infiltrating T cells, T-cell subsets, and Ia+ cells were found. With time PI, the density of infiltrating total T cells (Thy-1.2+), helper/inducer (Lyt-1+), and suppressor/cytotoxic (Lyt-2+) T cells increased; Lyt-1+ and Lyt-2+ cells were detectable in meningeal as well as parenchymal infiltrates, while later on, Lyt-1+ cells showed some predilection for the CNS parenchyma and Lyt-2+ cells for meninges. Ia+ cells (B cells, macrophages, activated T cells) were present in small numbers only. Ig+ cells (B cells and macrophages) appeared shortly before onset of signs and persisted in moderate numbers. These results reconfirm the importance of early T-cell involvement for the development of EAE; they might also indicate a secondary role for Ig+ cells and are consistent with the concept that presentation of myelin antigens to T cells might occur locally on Ia-bearing endothelial cells within the CNS.
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PMID:Acute experimental allergic encephalomyelitis in the mouse: immunopathology of the developing lesion. 257 95

Lines of thymus-derived lymphocytes reactive against bovine myelin basic protein (BP) were established in vitro from SJL/J mice. These lines are stable in long-term culture and mediate inflammatory central nervous system (CNS) lesions and a low incidence of clinical experimental allergic encephalomyelitis (EAE) when injected into recipient SJL/J mice. The line cells proliferate in response to BP of bovine, rat, or mouse origin. Clones were derived from these lines, and the characteristics of these clones were analyzed. The clones express Thy-1, Ly-1, and L3T4 antigens and are negative for Ly-T2. The clones all proliferate in response to bovine BP, with different clones showing varying degrees of cross-reactivity between bovine, rat, and mouse BP. The proliferative response is MHC-restricted; antigen-presenting cells from I-As strains are required. Compatible with their phenotype as helper cells, some of the clones will provide help to primed B cells stimulating antibody production in an in vitro assay. When injected into recipients pretreated with pertussis and irradiation, clones that showed proliferation to mouse BP induced the development of inflammatory lesions in the CNS, with mortality of 28% of the recipients. T cell lines were also established in (BALB/c x SJL/J)F1 mice. In contrast to the homozygous SJL/J lines, these lines were highly encephalitogenic, inducing a high incidence of clinical and histologic EAE when injected in vivo.
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PMID:Characterization of T cell lines and clones from SJL/J and (BALB/c x SJL/J)F1 mice specific for myelin basic protein. 257 39

Spirogermanium (SG) is a metal-containing compound reported to have antitumor, antiarthritic, antimalarial and immunoregulatory activity. In this study we have demonstrated that treatment of mice and rats with spirogermanium results in an inhibition of autoimmune disease and cell-mediated immune (CMI) responses. Prophylactic administration of SG inhibited the development of adjuvant-induced arthritis and the DTH response to purified protein derivative (PPD) in Lewis strain rats. SG treatment was also able to alleviate the symptoms of experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats. In two strains of mice, BDF1 and C57B1/6, the DTH response to sheep red blood cells could be suppressed by intraperitoneal (i.p.) administration of SG. The spleens of both mice and rats that have been treated with this drug contain suppressor cells which inhibit the response of normal cells to concanavalin A (Con A) and the mixed lymphocyte reaction. In addition, the generation of cytotoxic T cells (CTL) in the murine MLR is abrogated in the presence of these suppressor cells. The suppressor cells were radiation-resistant (2000 rad), indomethacin-insensitive and were not depleted by treatment with anti-Thy-1.2 antiserum plus complement. These results suggest that SG modulates cell-mediated immune responses in vivo by the induction of non-specific suppressor cells.
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PMID:Immunomodulatory activity and non-specific suppressor cell generation by spirogermanium in murine and rat models of cell-mediated immunity. 297 35

Allele-specific monoclonal anti-I-A antibodies are capable of specifically suppressing the immune response to antigens under the control of the allele towards which the antibody is directed, without suppressing the response to antigens under the control of the alternative allele of the I-A alpha and beta chain genes in an F1 heterozygote. This phenomenon, which has been termed 'allele-specific immunosuppression', is antigen-specific, long-lasting and transferrable with Thy-1-positive spleen cells. This type of immunosuppression has been applied to animal models of autoimmune disease, in both homozygous and heterozygous animal models. Anti-I-A monoclonal antibodies are capable of preventing, suppressing and treating experimental allergic encephalomyelitis (EAE), of partially suppressing experimental autoimmune myasthenia gravis, and of preventing the onset of type I insulin-dependent diabetes in the BB/W diabetic rat. In addition, this type of immunotherapy has succeeded in almost completely suppressing nephritis in NZB X NZW F1 mice, which normally develop severe lupus-like nephritis. Significant toxicity, which may be due to anti-allotype antibodies, anti-idiotype antibodies, or to impurities in the monoclonal antibody preparations, has been encountered in the BB/W diabetic rat. In addition, attempts to extend these observations to EAE in the cynomolgus monkey have encountered significant mortality which appears to be attributable to the monoclonal antibody injections (anti-HLA-DR). The mechanism of this toxicity and means of circumventing it are currently under investigation. These results demonstrate the critical role of I-A molecules in the induction and continuance of the autoimmune process in these experimental animal models.
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PMID:Monoclonal anti-Ia antibody therapy in animal models of autoimmune disease. 331 1


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