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)

The effectiveness and the mechanism of T cell vaccination were studied in two experimental models of autoimmune disease. The attempt to modulate autoimmune disease via idiotypic regulation of autoreactive antigen-specific T cells was first shown in the rat experimental autoimmune encephalomyelitis (EAE) model where inactivated EAE-inducing T cells could both immunize and protect rats from EAE. We previously reported that low dose T cell vaccination against EAE in Lewis rats was immunologically specific, long lasting and extremely efficient in preventing adoptive transfer of the disease. In experimental autoimmune uveitis (EAU) T cell vaccination was also found to be effective. In both cases, antigen or mitogen activation of the T cells prior to inoculation was required. In the EAE model, T cell vaccination appeared to be associated with two sets of T lymphocytes (CD4+ CD8- helper and CD4- CD8+ cytotoxic/suppressor cells) which were cloned and found to be specifically reactive to the vaccine cells. These anti-idiotypic T cell clones were able to antagonistically modulate the in vitro proliferation of encephalitogenic Z1a cells. In vivo, transfer of the lymph node cells (from which the anti-idiotypic clones were derived) from vaccinated animals to naive syngeneic recipients conferred resistance to EAE. In the EAU model, we also found a consistent immunological response raised against different activated T cells (four T cell lines with irrelevant specificities and mitogen-activated lymphoid cells) in addition to the anti-idiotypic cells. This response, apparently directed to T cell activation markers, might combine with the anti-idiotypic response to regulate autoimmunity.
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PMID:T cell vaccination in autoimmune diseases. 179 4

We previously demonstrated that encephalitogenic CD4+ T lymphocytes from the long-term cultured line S1, specific for myelin basic protein, induce a CD8+ T cell population in vivo that protects naive Lewis rats against experimental autoimmune encephalomyelitis caused by S1 cells. In order to determine the contribution of individual T cell population in the development of induced resistance, we have analyzed the in vitro proliferative capacity of phenotypically distinct T cell populations isolated from S1-immunized rats. We found that both CD8+ and CD8-CD4- T cells show striking proliferative responses when stimulated with S1 cells, whereas CD4+ T cells show only minimal responses. In addition, a significant proportion of the CD8-CD4- cells, after stimulated by S1 cells, became CD8+ and had a strong cytolytic activity toward S1 cells. These results suggest a contribution of double-negative splenic T cells in the regulatory circuit associated with autoimmune encephalomyelitis.
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PMID:CD4-CD8- splenic T cells from Lewis rats recovered from experimental autoimmune encephalomyelitis respond to encephalitogenic T cells that mediate this disorder. 190 33

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

To study T cell and macrophage activity during measles, levels of interferon-gamma (IFN-gamma) and neopterin in plasma and cerebrospinal fluid (CSF) were measured. Plasma levels of IFN-gamma were elevated in measles (1.17 +/- 0.27) compared with healthy adults (0.13 +/- 0.06, P less than .05) and children (0.14 +/- 0.06, P less than .01). Plasma levels of neopterin were elevated in measles (32.5 +/- 2.7) compared with healthy adults (5.3 +/- 2.9, P less than .0001), healthy children (12.1 +/- 4.0, P less than .001), and children with other infectious diseases (20.6 +/- 4.0, P less than .02). IFN-gamma was increased in measles primarily during rash; neopterin remained elevated for several weeks. Levels of neopterin showed a significant positive correlation with plasma levels of soluble interleukin-2 receptor and soluble CD8, two other parameters of T cell activation. Children with measles complicated by pneumonia had higher levels of neopterin in serum than those with uncomplicated disease. Children with measles complicated by autoimmune encephalomyelitis had higher levels of neopterin in CSF than those with noninflammatory neurologic disease but lower than those with central nervous system infections. Thus, IFN-gamma seems to be produced in vivo during acute measles virus infection; deficiency of this lymphokine does not appear to correlate with increased susceptibility to secondary infections.
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PMID:Immune activation during measles: interferon-gamma and neopterin in plasma and cerebrospinal fluid in complicated and uncomplicated disease. 210 64

The ability to prevent the expression of retinal SAg induced experimental autoimmune uveitis (EAU) in Lewis rats by oral administration of the SAg and SAg fragments was investigated. Oral administration of the SAg molecule prevented or markedly diminished the clinical appearance of SAg-induced disease as measured by ocular inflammation. Furthermore, oral administration of the SAg also markedly diminished uveitis induced by the uveitogenic M and N fragments of the SAg. M and N fragments were not effective in preventing SAg-induced EAU, although feeding the M fragment prevented disease induced by the M fragment. Oral administration of the SAg did not prevent myelin basic protein induced experimental autoimmune encephalomyelitis, whereas feeding myelin basic protein did. In vitro studies demonstrated a significant decrease in proliferative responses to the SAg in lymph node cells draining the site of immunization from fed vs nonfed animals. Furthermore, the addition of splenocytes from SAg-fed animals to cultures of a CD4+ SAg-specific cell line profoundly suppressed the cell line's response to the SAg, whereas these splenocytes had no effect on a purified protein derivative-specific cell line. The Ag-specific in vitro suppression was blocked by anti-CD8 antibody (OX-8) demonstrating that this suppression is dependent on CD8+ T-cells. These experiments demonstrate that Ag-specific immunomanipulation can be achieved in the EAU model by oral administration of the SAg and raise the possibility that such an approach may have practical clinical implications in uveitis as well as other human autoimmune diseases.
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PMID:Inhibition of S-antigen induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-antigen. 213 41

Immune abnormalities, including deficient CD8 lymphocyte-mediated suppression, have been implicated in the progression of multiple sclerosis (MS). The peripheral sympathetic branch of the autonomic nervous system innervates the lymphoid organs and affects immune function. Animals with an ablated sympathetic nervous system develop more severe experimental allergic encephalomyelitis than control animals and exhibit an increased density of beta-adrenergic receptors on their lymphocytes. Experimental allergic encephalomyelitis shares many features with MS. Accordingly, we investigated the psychogalvanic skin reflex in patients with rapidly progressive MS and found that 13 patients (57%) lacked this sympathetic-mediated response. The density of beta-adrenergic receptors on lymphocyte subsets was increased in progressive MS, most notably on the CD8 suppressor/cytotoxic subset. B lymphocytes had the greatest number of receptors with 12.1 +/- 1.8 fmol/10(6) cells in control subjects and 18.7 +/- 2.6 fmol/10(6) cells in patients with MS. CD8 lymphocytes possessed an intermediate number of receptors with 3.4 +/- 0.4 fmol/10(6) cells in control subjects and 9.1 +/- 1.6 fmol/10(6) cells in patients with MS. CD4 lymphocytes demonstrated the fewest receptors with 1.2 +/- 0.1 fmol/10(6) cells in control subjects and 1.8 +/- 0.4 fmol/10(6) cells in patients with MS. No differences in the affinity or function (cyclic adenosine monophosphate levels in response to 10(-5) M (-)isoproterenol) of the adrenergic receptor were found when patients with progressive MS and control subjects were compared. Autonomic abnormalities in progressive MS and the increased beta-adrenergic receptor density found on CD8 lymphocytes may be related.
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PMID:Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis. 216 44

T-cell clones have been isolated from SJL/J mice after immunization with myelin proteolipid protein (PLP). The cloned cells responded strongly to PLP stimulation in vitro as well as to the synthetic PLP-related peptide 139-151. The response to PLP is Ia mediated, since it was inhibited by monoclonal antibodies to the matched I-As haplotype, but not with antibodies to other I-A haplotypes. Phenotypic analysis using immunofluorescence demonstrated the following characteristics of the clones: Thy-1+, CD4+, CD5+ and CD8-. Injection of 10-30 million PLP-activated cells from one clone induced severe experimental allergic encephalomyelitis in five mice, both clinically and histologically. This represents to our knowledge the first report of PLP-specific encephalitogenic cloned T cells.
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PMID:The development and characterization of encephalitogenic cloned T cells specific for myelin proteolipid protein. 229 82

We examined frozen sections of frontal cortex, medulla, and dorsal root ganglia from a patient with small-cell lung cancer and paraneoplastic encephalomyelitis, involving the medulla and dorsal root ganglia, with a panel of antibodies reactive for IgG, IgM, C3, B cells, T cells, T cell subsets, macrophages, and class I and II (HLA-DR) major histocompatibility complex (MHC) antigens. We detected an antineuronal antibody (anti-Hu) in the serum and CSF of the patient and found deposits of IgG in the periphery of some neurons in dorsal root ganglia. The infiltrates were almost exclusively T cells with a predominance of CD8-positive cells. Neurons did not express class I or II MHC antigens. Satellite cells in the dorsal root ganglia from the patient and controls were HLA-DR-positive. These data indicate that CD8-positive T cells predominate in the inflammatory infiltrates of paraneoplastic encephalomyelitis. IgG deposits may be relevant in the damage of the sensory neurons.
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PMID:Immunohistochemical analysis of the immune reaction in the nervous system in paraneoplastic encephalomyelitis. 223 46

The in vivo administration of monoclonal antibody (mAb) to the CD4 antigen associated with helper T cells has been successful in prolonging the survival of nonhuman primates with experimental allergic encephalomyelitis (EAE). EAE was induced in 17 outbred longtailed macaques (Macaca fascicularis) by inoculation of homologous myelin basic protein (BP) in complete Freund's adjuvant (CFA). Treatment was begun at the onset of clinical signs. Eleven animals were treated with anti-CD4 mAb Leu3a (eight) or OKT4a (three). Of the six control animals, two received anti-CD8 mAb (Leu2a), and four were treated with saline. Specific T- and B-cell subsets which have been implicated in the development of EAE were monitored throughout the course of the disease by one- and two-color immunofluorescence (IF). The monkey anti-BP antibody and anti-mouse immunoglobulin (IgG) responses were measured by enzyme-linked immunoassay (ELISA) techniques, as were the levels of free-circulating murine IgG. The nature of the infiltrating lymphocytes in the brain was evaluated histologically post mortem. Our results indicate that anti-CD4 mAb can prolong survival and in some cases completely reverse the clinical appearance of the disease; however, relapses did occur. Treatments with Leu3a or OKT4a anti-CD4 mAbs reversed the ongoing depletion of CD4+ and CD8+ cells caused by the development of EAE and appeared to reduce the size and degree of inflammation in brain lesions. These treatments did not induce immunologic tolerance to mouse IgG since all of the anti-CD4-treated animals produced high titers of anti-mouse IgG antibodies. Treatment with Leu2a (anti-CD8) had no effect on the development of EAE. These results suggest that CD4+ cells are important to the pathogenesis of EAE in macaques and that manipulation of this subset with monoclonal antibodies may provide effective treatment of human demyelinating disease.
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PMID:In vivo administration of anti-CD4 monoclonal antibody prolongs survival in longtailed macaques with experimental allergic encephalomyelitis. 244 10


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