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)

T cells are considered to be of prime importance in immune regulation of both B and T cell functions. The targets of recognition in T-T cell interactions are not clear. Most recent experimental work has focused on the idiotypic regulatory interactions mediated by TCR peptides. There is experimental evidence that regulatory cells exist that do not recognize the TCR. This type of regulation is selectively induced by activated T cells. Therefore, we designed this study to examine the possible role of cytokine receptors as targets of immune regulation. We tested two peptides of IL-2R alpha-chain, 2 of IL-2R beta-chain, and one of TNFR (p60). All peptides were found to be immunogenic at inducing T cell proliferation and four induced Abs in Lewis rats. We generated T cell lines to these five peptides, and tested them both in vitro and in vivo. We found that the T cells exhibited a proliferative response when cultured with activated, irradiated stimulator cells that were augmented upon addition of the cytokine receptor peptide. The cytokine profile of the lines was characterized as well as the Vbeta gene composition. One of the lines significantly protected against active encephalomyelitis. These results point at cytokine receptors as possible targets of immune regulation and T-T cell interactions.
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PMID:IL-2 and TNF receptors as targets of regulatory T-T interactions: isolation and characterization of cytokine receptor-reactive T cell lines in the Lewis rat. 894 88

Experimental allergic encephalomyelitis (EAE) is inducible in experimental animals immunized with myelin basic protein (MBP), proteolipid protein (PLP) or their peptides. We compared T-cell responses to encephalitogenic epitopes of PLP(43-64) and MBP(Ac1-11) in a single mouse strain, (PL/J x SJL)F1. MBP(1-11)-specific T-cell hybridomas expressed predominantly TCR V beta 8 or V beta 4, while PLP(43-64)-specific hybridomas expressed a diverse TCR repertoire. To analyze the biologic significance of the TCR repertoire (limited vs. diverse) to disease susceptibility, we pretreated mice with a superantigen (SEB), and then induced disease with these autoantigens. Mice injected with SEB and immunized with MBP(Ac1-11) showed significant inhibition of EAE, whereas SEB-pretreated mice immunized with PLP(43-64) had an increased severity of EAE and developed a chronic disease. These data demonstrate that prior exposure to microbial superantigens can significantly alter the autoimmune disease course depending upon the TCR repertoire used by the autoantigen.
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PMID:Prior exposure to superantigen can inhibit or exacerbate autoimmune encephalomyelitis: T-cell repertoire engaged by the autoantigen determines clinical outcome. 898 96

Recently, it has been shown that the immunization of mice with an 18 amino acid synthetic peptide corresponding to the third hypervariable region of MHC class II beta chain can induce a specific antibody response against MHC class II molecules, and can be utilized in the prevention and treatment of experimental allergic encephalomyelitis (EAE) [Proc. Natl. Acad. Sci. 1994, 91, 8005-8009]. Based on this finding, a chemically-modified synthetic peptide with the amino acid sequence corresponding to residues of beta 57-76 from human HLA-DR4Dw4 (DR4/1 peptide) is being clinically investigated for the treatment of rheumatoid arthritis in human. The present study describes the development of a novel in vitro potency assay for human HLA-DR4/1 peptide using cloned murine T-T hybridoma cells. Several mouse strains were immunized with the DR4/1 peptide and their lymph node T cell proliferation was measured in the presence of syngeneic APCs and the DR4/1 peptide. T cells isolated from the peptide primed-B10. PL mouse strain, which showed the highest recall response in this assay, were fused with BW5147 lymphoma cells to generate DR4/1 peptide-specific T-T hybridoma clones. Cloned hybridoma cells were characterized for peptide specificity and MHC class II restriction, and used to monitor the biological activity of various DR4/1 peptide preparations. The potency of peptide batches were assessed by measuring the IL-2 secretion of cloned T-T hybridoma cells upon TCR engagement in an antigen-specific manner. The quantitative detection of IL-2 was performed by measuring [3H]thymidine incorporation of HT-2 cells or directly by ELISA. These results demonstrate that peptide-specific murine T-T hybridoma clones can be successfully utilized to monitor biological activity of synthetic peptides by measuring T cell-mediated immunological responses. Development of such in vitro potency assay for synthetic peptides may have broad applications for vaccines related to immunological disorders.
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PMID:Application of murine T-T hybridoma cells to in vitro potency assay of human synthetic peptide vaccines. 900 39

This study investigated the role of gamma delta T cells in experimental allergic encephalomyelitis (EAE), a chronic inflammatory disease of the central nervous system (CNS) that resembles multiple sclerosis. The strategy was to assess the effect on EAE of TCR peptide immunization directed against V gamma 6 T cells, shown recently to predominate in the CNS of mice during the early stages of EAE. The data show that TCR peptide immunization specific for V gamma 6 chains does not induce protection against EAE, since the incidence of EAE in TCR treated animals was similar to control mice, and therefore does not affect disease susceptibility per se, but rather alters the development of the disease. Specifically, there was a delay in the onset of EAE and a reduction in disease severity in TCR treated animals, although the effects were not highly significant. These findings suggest a role for gamma delta T cells in the development of EAE; however, further studies are necessary to confirm the specificity of TCR peptide immunization.
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PMID:Modulation of experimental allergic encephalomyelitis in mice by immunization with a peptide specific for the gamma delta T cell receptor. 904 40

Our analysis of TCR V gene usage in mice transgenic for the V beta 8.2 gene has demonstrated that T cells isolated from the spinal cord of these transgenic mice during active experimental autoimmune encephalomyelitis were significantly biased for V alpha 2 expression. This V alpha 2 bias was noted in T cells derived from the periphery as well but only after stimulation with specific antigen. Thus, spinal cord-derived pathogenic T cells had already undergone activation and expansion within the central nervous system environment of these mice. As part of an investigation of regulatory function in these V beta 8.2 transgenic mice, two T cell lines were selected. The first T cell line is encephalitogenic and specific for the dominant myelin basic protein peptide NAc1-11, while the second T cell line is specific for the V beta 8.2 protein. Surprisingly, polymerase chain reaction and sequence analysis of the TCR from both the T cell lines demonstrated that they utilize identical V beta, D beta, J beta, and V alpha gene segments. The only difference found was in their use of the J alpha gene segment, indicating that this region of the TCR molecule can play a key role in determining antigen specificity.
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PMID:Myelin basic protein-specific and TCR V beta 8.2-specific T-cell lines from TCR V beta 8.2 transgenic mice utilize the same V alpha and V beta genes: specificity associated with the V alpha CDR3-J alpha region. 906 58

To test the effects of insulin-like growth factor-I (IGF-I) on clinical deficits, lesion severity, and immune cell response in acute, non-demyelinative experimental autoimmune encephalomyelitis (EAE), we induced EAE in Lewis rats by passive transfer of an MBP-reactive T lymphocyte line. Four days after receiving 5 x 10(5) MBPL-1 T cells intravenously, ten pairs of rats had the same mild degree of tail and hind limb weakness. Ten were given 300 micrograms IGF-I i.v. twice daily for 6 days, and the other 10 received the same volume of 0.89% NaCl. Pairs of rats were sacrificed after 4 days and 6 days of IGF-I and placebo treatment and spinal cord sections were processed for immunostaining, in situ hybridization, and morphological examination. IGF-I treatment decreased clinical deficits, lesion numbers, and lesion areas significantly. Numbers of CD4-positive T cells, alpha/beta TCR-positive cells, and ED-1-positive macrophages were also significantly reduced by IGF-I treatment. Similar reductions were found in our second trial, when 11 days of placebo and IGF-I injections began the day after transfer. No demyelination was observed in either toluidine blue-stained semithin sections or sections immunostained with an antibody raised against myelin basic protein (MBP). We conclude that IGF-I-induced reductions in immune cell responses can occur in the absence of demyelination and are of major importance in decreasing clinical deficits and lesion severity in EAE. If IGF-I has similar effects in multiple sclerosis, we think that it will be useful therapeutically.
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PMID:Insulin-like growth factor-I treatment reduces immune cell responses in acute non-demyelinative experimental autoimmune encephalomyelitis. 906 62

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease inducible by encephalitogenic helper T cells expressing V beta 8.2. In this study, we examined the relationship between the stressor-induced alternation of clinical EAE and the induction of autoreactive T cells using Lewis rats. Animals were immersed for 5 min in a water bath maintained at 44 degrees C continuously for 10 or 13 days, before or after the immunization of the encephalitogenic peptide, respectively. Stress administrations after the immunization clearly diminished the severity of clinical EAE, and delayed the onset of disease. On the other hand, stress administrations prior to the immunization resulted in the marginal suppression of clinical EAE. Splenocytes of the stressed rats showed, however, comparative proliferative responses to the encephalitogenic peptide or mitogens with that of the control rats. Moreover, higher level of V beta 8.2 mRNA expression was detected in the spinal cords of the stressed rats than in control rats. Sequence analysis of CDR3 region of TCR cDNA showed that V beta 8.2+ T cells in the spinal cords of the stressed rats possess common features with the biased encephalitogenic T cells. These results suggest that the stressor-induced suppression of clinical EAE is not simply because of the failure of induction of autoreactive T cells, nor localization of the autoreactive T cells in the central nervous system.
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PMID:Stress down-regulates experimental allergic encephalomyelitis (EAE) but permits activation and localization of autoreactive V beta 8.2+ T cells. 913 55

To investigate TCR V alpha gene expression in the Lewis rat model of experimental autoimmune encephalomyelitis, we obtained V alpha chain sequences from two V beta8.2+-encephalitogenic, BP72-89-specific T cell clones. Two different V alpha genes, a V alpha2 gene and a V alpha23 gene, are utilized, but both were found to contain an asparagine repeat (Asn3+) sequence present in the V alpha CDR3 region. This Asn3+ motif is also present in the previously reported sequence of a BP68-88-specific hybridoma, 510, which utilizes a different V alpha2 gene family member. In further experiments, spinal cord T cells were isolated at the onset of basic protein (BP)-induced disease and sorted for the OX-40 activation marker, which we have previously used to enrich for specifically activated T cells. Analysis of V alpha expression in the OX-40+ population revealed the biased use of three V alpha genes, V alpha1, V alpha2, and V alpha23. The Asn3+ motif was present in the V alpha CDR3 region of V alpha1, V alpha2, and V alpha23 cDNA derived from OX-40+ spinal cord T cells but found to be generally absent in the OX-40- spinal cord population. Since these Asn3+ motif-bearing V alpha chain sequences are nearly identical to those utilized by the BP-specific encephalitogenic clones described, it is likely that these V alpha sequences are derived from disease-associated T cells in the spinal cord. Thus, we demonstrate that the Asn3+ V alpha CDR3 motif is strongly associated with experimental autoimmune encephalomyelitis in the Lewis rat and propose that it plays a role in TCR recognition of a specific BP peptide/MHC complex.
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PMID:A TCR V alpha CDR3-specific motif associated with Lewis rat autoimmune encephalomyelitis and basic protein-specific T cell clones. 916 70

The combination of genetic and environmental factors that contribute to human autoimmune responses has made potential triggers of these diseases difficult to identify. We examined how experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, is triggered using TCR-transgenic mice specific for myelin basic protein (MBP). In these TCR-transgenic mice, EAE can be actively induced and also occurs spontaneously. The incidence of spontaneous EAE in this model is largely confined to adolescence and early adulthood and is more prevalent among males than females, indicating that hormonal influences may contribute to triggering central nervous system autoimmune disease. Disease induction studies show that not all stimuli that activate MBP-specific T cells in vivo also induce EAE. Immunization with MBP peptide stimulates the transgenic T cells to produce Th1 cytokines; however, the activated T cells do not accumulate in the central nervous system and induce EAE unless pertussis toxin is also administered. EAE can be induced by intrathecal injection of either stimulated or nonstimulated transgenic T cells into nontransgenic or transgenic recipients. Therefore, gaining access to the central nervous system appears to be the critical step in this model for the induction of EAE, regardless of the activation state of the T cells.
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PMID:Triggers of autoimmune disease in a murine TCR-transgenic model for multiple sclerosis. 920 Apr 91

Chronic inflammatory autoimmune diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis are caused by CD4(+) Th1 cells. Because Th2 cells antagonize Th1 cell functions in several ways, it is believed that immune deviation towards Th2 can prevent or cure autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease used as a model for multiple sclerosis. Using an adoptive transfer system we assessed the role of Th1 and Th2 cells in EAE. In vitro generated Th1 and Th2 cells from myelin basic protein (MBP)-specific TCR transgenic mice were transferred into normal and immunodeficient mice. Th1 cells caused EAE in all recipients after a brief preclinical phase. Surprisingly, Th2 cells also caused EAE in RAG-1 KO mice and in alphabeta T cell-deficient mice, albeit after a longer preclinical phase. Normal or gammadelta T cell-deficient mice were resistant to EAE induced by Th2 cells. The histopathological features of this disease resembled those of an allergic process. In addition, disease induction by Th1 cells was not altered by coadmininstration of Th2 cells in any of the recipients. These findings indicate that MBP-specific Th2 cells have the potential to induce EAE and that the disease induced by previously activated Th1 cells cannot be prevented by normal lymphocytes nor by previously activated Th2 cells.
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PMID:Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease. 922 60


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