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)

We have shown previously that treatment of SJL/J mice with anti-interferon-gamma monoclonal antibody (mAb) exacerbated experimental allergic encephalomyelitis (EAE) only if administered at the time of encephalitogenic challenge. Here we investigate the role of interferon-gamma (IFN-gamma) and anti-IFN-gamma mAb in the early events of T cell activation in vitro. Pretreatment of murine peritoneal exudate cells (PEC) with IFN-gamma led to a significant increase in their ability to activate myelin basic protein (MBP)-specific, short-term T cell lines. When exogenous IFN-gamma was added to cocultures of T cells and MBP-pulsed PEC, the antigen-specific T cell proliferation was considerably reduced. Anti-IFN-gamma mAb added to these cultures neutralized the inhibitory effect of the exogenous IFN-gamma on T cell proliferation but had no visible effect on class II MHC expression by the antigen-pulsed PEC present in the same cultures. A reduction in T cell proliferation was also observed when the T cells were treated with IFN-gamma prior to coculture with the MBP-pulsed PEC. These results demonstrate that, on one hand, IFN-gamma enhances the ability of PEC to induce antigen-specific T cell proliferation but, on the other hand, acts on the T cells themselves by inhibiting their proliferation in response to the antigen-pulsed PEC. This may explain why treatment with anti-IFN-gamma antibody in vivo induces EAE exacerbation.
Cell Immunol 1992 Dec
PMID:Effect of interferon-gamma on myelin basic protein-specific T cell line proliferation in response to antigen-pulsed accessory cells. 128 May 34

To characterize the cellular immune response in an autoimmune lesion, we investigated the accumulation of specific T cells in the central nervous system in actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats, using a limiting dilution analysis (LDA) assay for T cells that proliferate in response to antigens. Lymphocytes isolated from the spinal cord infiltrate were compared with cells from the popliteal lymph nodes with respect to frequency of cells responding to basic protein (BP), mycobacterium tuberculosis (MT), the 65-kD heat shock protein (hsp65), allogeneic brown norway spleen cells, and concanavalin A. Additionally, we compared the BP frequency in acute EAE of cells from the spinal cord, peripheral blood, spleen and lymph nodes, and the spinal cord and lymph node after recovery from EAE. We found that acute EAE was associated with marked enrichment of BP-reactive T cells in the spinal cord relative to their frequency in the lymphoid organs and peripheral blood. The infiltrate was also enriched for T cells responding to hsp65; alloreactive T cells, in contrast, were not enriched. The frequency of BP reactive T cells in the spinal cord was highest at the peak of paralysis; however, BP-reactive T cells could still be detected at moderate frequencies after clinical recovery. We established BP- and Mycobacteria-reactive T cell lines from the spinal infiltrates that were CD4+ and TcR alpha beta +. Most of the BP lines were found to react to the major encephalitogenic epitope of guinea pig BP for rats (amino acids 71-90); these lines were found to mediate EAE in naive recipients. T cell lines recognizing other epitopes of BP were not encephalitogenic. All of the lines responsive to Mycobacteria recognized hsp65 or hsp70. These results indicating that the immune infiltrate in active EAE is enriched with cells responding to the autoantigen and to hsp65 were confirmed in EAE adoptively transferred by anti-BP T cell clone.
J Clin Invest 1992 Dec
PMID:T cells in the lesion of experimental autoimmune encephalomyelitis. Enrichment for reactivities to myelin basic protein and to heat shock proteins. 128 35

We performed immunocytochemical studies to analyze the inflammatory infiltrate and major histocompatibility complex class II (Ia) antigen expression in the spinal cord of Lewis rats with acute experimental allergic encephalomyelitis (EAE) induced by inoculation with myelin basic protein and adjuvants. Using antibodies to lymphocyte markers and other monoclonal antibodies we found that during clinical episodes the inflammatory infiltrate was chiefly composed of T lymphocytes and macrophages. The majority of cells in the inflammatory infiltrate were stained by the W3/25 antibody to CD4 and a proportion was stained by OX22 which labels the high molecular weight form of the leucocyte common antigen (CD45RC). CD8+ T cells were sparse and B cells were not detected. There was minimal staining with the OX39 antibody to the interleukin-2 receptor. Presumptive microglia, identified by their dendritic morphology, expressed Ia antigen during the clinical episodes and after recovery. The prominence of Ia antigen expression after recovery could indicate that this Ia expression was associated with downregulation of the encephalitogenic immune response. We also performed flow cytometry studies on cells extracted from the spinal cord of rats before and during attacks of EAE. With flow cytometry, we found that in established disease a mean of 83(SD, 23)% of CD2+ cells were CD4+, and a mean of 27(SD, 12)% of CD2+ cells were CD45RC+. In rats sampled on the first day of signs, a mean of 43(SD, 22)% of CD2+ cells were CD45RC+. In the cells extracted from the spinal cord of rats with established disease a mean of 47(SD, 32)% of macrophages were CD45RC+. Our study has combined an immunocytochemical assessment of tissue sections with quantitative flow cytometry assessment of cells extracted from the spinal cord of rats with acute EAE. We have shown that the majority of T lymphocytes in the spinal cord are CD45RC-. We have also found prominent Ia expression on dendritic cells in acute EAE and after clinical recovery.
J Neurol Sci 1992 Dec
PMID:Expression of CD45RC and Ia antigen in the spinal cord in acute experimental allergic encephalomyelitis: an immunocytochemical and flow cytometric study. 133 96

The results of a serological survey of a free-living population of meadow voles (Microtus pennsylvanicus) in Pinawa, Manitoba (Canada) showed that these animals possessed antibodies to six of the eleven viruses tested for, namely: reovirus type 3, murine encephalomyelitis agent, ectromelia virus, murine adenovirus, murine hepatitis virus and lymphocytic choriomeningitis virus. The significant increase in the number of individuals possessing specific antibodies suggests that these viruses, or related viruses, may be responsible for the decline in the population studied.
Rev Sci Tech 1992 Dec
PMID:[Serological study of the incidence of murine viruses in a population of small wild rodents (Microtus pennsylvanicus Ord, 1815)]. 133 64

Most studies suggest that the pathogenesis of Multiple Sclerosis (MS) is based on immune mechanisms of myelin injury. In addition, a viral infection, possibly established in the first few years of the patient's life, may be crucial in setting the stage for such immune mediated injury when acting on the appropriate genetic background. Of the several models of virus-induced demyelination described in the last two decades, Theiler's murine encephalomyelitis virus (TMEV) infection has emerged as one of the best models for MS.
Ital J Neurol Sci 1992 Dec
PMID:The immunopathogenesis of a viral model of multiple sclerosis: Theiler's virus induced demyelination. 134 36

Lyme disease, like syphilis, a spirochetal infection, can appear with exacerbations and remissions in different stages. The clinical picture is marked by dermatological, neurological, rheumatic and cardiological complications. PNS complications appear in the second and third stage. Tick bite meningoradiculoneuritis neuritis (Garin-Bujadoux-Bannwarth-Syndrome), characterized by painful asymmetrical sensory and motor dysfunctions and inflamed CSF, is a typical manifestation of the second stage. Mononeuritis multiplex appearing in conjunction with acrodermatitis chronica atrophicans is a typical PNS manifestation of the third stage. CNS involvement may also occur in early and late stages of Lyme-Borreliosis, presenting as myelitis or progressive encephalomyelitis. Lyme-Borreliosis is a treatable condition, which should not be missed in the differential diagnosis of PNS and CNS disorders.
Ital J Neurol Sci 1992 Dec
PMID:Neurological complications of Lyme borreliosis. 134 45

The dominant immune response to rat myelin basic protein in H-2u mice is directed against the acetylated, N-terminal peptide Ac1-11 (AcASQKR-PSQRHG). This peptide causes encephalomyelitis on injection into mice of the H-2u haplotype. Only two residues of the peptide are required for ligation of the TCR from an Ac1-11-specific T cell hybridoma. Proline at position 6 could not be substituted by any other L-amino acid, whereas glutamine at position 3 could be replaced by phenylalanine, histidine, methionine, or tyrosine. Cross-reactive recognition of these residues appears to be specific, because increasing the affinity of each analogue for its MHC restriction element, by replacing lysine with tyrosine at position 4, did not alter the pattern of cross-reactivity. For the majority of substitutions at this position, a lack of stimulation could not be explained by failure to bind to I-Au. However, competition binding studies showed that introduction of proline at position 3 reduced the efficacy of binding to I-Au. Cross-reactive analogues of Ac1-11 were injected into H-2u mice to test the extent to which cross-reactive T cell activation might lead to autoimmune disease in this model. An analogue containing methionine at position 3 caused clinical experimental autoimmune encephalomyelitis in a small percentage of H-2u mice.
J Immunol 1992 Dec 01
PMID:Cross-reactive antigen recognition by an encephalitogenic T cell receptor. Implications for T cell biology and autoimmunity. 138 32

In addition to myelin basic protein (MBP) and proteolipid protein (PLP), oligodendrocyte (Od) membrane autoantigens, such as the glycoprotein M2/MOG, could participate in the pathogenesis of autoimmune demyelinating diseases of the central nervous system (CNS), such as experimental allergic encephalomyelitis (EAE) or multiple sclerosis (MS). We have described an Od-specific autoreactive and cytotoxic T-cell clone, named C2, which recognized M2/MOG without conventional MHC restriction. In order to analyse the Od/C2 interaction, we determined the alpha/beta T-cell receptor (TCR) variable region usages and structures of C2. Monoclonal antibody stainings of C2 and nucleotide sequences show that the alpha chain is composed of a V alpha 5 and a J alpha identical to J alpha 18BBM142 gene segments, and that the TCR beta chain is composed of V beta 17a, D beta 2.1 and J beta 2.2 gene segments indicating that C2 used a conventional alpha/beta TCR for M2/MOG recognition.
Scand J Immunol 1992 Dec
PMID:T-cell receptor identification of an oligodendrocyte-specific autoreactive cytotoxic T-cell clone without self restriction. 146 26

Chronic relapsing experimental allergic encephalomyelitis (CREAE) can be reproducibly induced in Biozzi AB/H mice following injection of spinal cord homogenate (SCH) emulsified in complete Freund's adjuvant (CFA). Active clinical disease is associated with mononuclear cell infiltration of the central nervous system (CNS), mainly the spinal cord. Whole brain homogenate (BH), however, failed to induce clinical or histological disease. In contrast, substituting sciatic nerve homogenate in the inoculum induced experimental allergic neuritis (EAN). Clinical disease was manifest earlier (13.1 +/- 0.3 days) than CREAE (16.2 +/- 1.4) and was accompanied by mononuclear infiltration of the peripheral nervous system (PNS). In comparison to CREAE induction, pretreating mice with SCH or BH in incomplete Freund's adjuvant (IFA) suppressed the development of SCH-induced disease. The BH was more tolerogenic than the SCH and this hyporesponsiveness was CNS antigen-specific as PNS tissue failed to inhibit the course of CREAE. Tolerance induced by pretreatment with SCH or BH in IFA was reversed by a single injection of 200 mg/kg cyclophosphamide, 2 days prior to CREAE induction. This suggests that IFA-induced hyporesponsiveness is actively regulated, possibly via the action of suppressor cells. In addition, treatment with neuroantigens in IFA appears to be mainly afferent acting as it serves to prevent initial disease induction. This treatment after immunization for CREAE, however, fails to prevent disease progression. Furthermore, treatment with CNS antigens emulsified in IFA during the post-acute remission stage appeared to synchronize and induce (32 +/- 1 days) the onset of clinical relapse, compared with untreated controls (41 +/- 5 days). This indicates that such IFA treatment has minimal value in controlling an ongoing immune disease of the CNS.
J Neuroimmunol 1992 Dec
PMID:Inhibition of chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse. 146 77

Infectious agents have often been implicated in the etiology of autoimmune diseases. Here we show that bacteria may also play a role in resistance to autoimmune diseases. SJL/J and (SJL/J x BALB/c)F1 mice are genetically susceptible to induction of experimental autoimmune encephalomyelitis (EAE), a murine model for human demyelinating autoimmune diseases such as multiple sclerosis. We studied the effect of several bacteria on the development of EAE and found that exposure of SJL/J or (SJL/J x BALB/c)F1 mice to Mycobacterium tuberculosis or Bordetella pertussis consistently rendered mice highly refractory to subsequent induction of the disease. Other bacteria such as Escherichia coli, Shigella and Staphylococcus aureus were found to be less effective, or were protective only if specific immunization procedures were used. Furthermore, M. tuberculosis and B. pertussis were protective irrespective of the route of administration and minute amounts (as low as 0.5 micrograms) of M. tuberculosis were sufficient to protect EAE-susceptible mice against induction of the disease. Interestingly, these bacteria, which are commonly used to promote development of EAE, conferred the highest degree of protection against the disease. The M. tuberculosis-induced protection was found to be associated with active suppression mechanisms mediated by T lymphocytes capable of transferring protection to naive syngeneic mice. These findings indicate that certain bacteria may protect against the development of autoimmune diseases. These results also suggest the potential use for still-unidentified bacterial agents in the manipulation of certain autoimmune diseases.
J Autoimmun 1992 Dec
PMID:Bacterial agents protect against autoimmune disease. I. Mice pre-exposed to Bordetella pertussis or Mycobacterium tuberculosis are highly refractory to induction of experimental autoimmune encephalomyelitis. 148 83


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