UMLS:C0014070 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0014070 (encephalomyelitis)
13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SJL mice immunized with proteolipid protein (PLP) develop relapsing experimental autoimmune encephalomyelitis (R-EAE). R-EAE is a CD4+, Th1 cell-mediated demyelinating disease of the central nervous system (CNS) that is used as a model for the human disease multiple sclerosis (MS). Previous studies showed that young (< 8 weeks) male SJL mice were resistant to active induction of EAE with CNS homogenate, while female mice were susceptible. We have recently observed that young male SJL mice immunized with a major encephalitogenic peptide of myelin, PLP 139-151, developed initial clinical and histological symptoms of EAE with a severity similar to age-matched females; however, unlike females, male mice did not relapse. Significant T cell proliferation to PLP 139-151, but not to other PLP and myelin basic protein (MBP) epitopes, was observed in both males and females during the initial episode, recovery, and first relapse of clinical disease. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of lymphokine mRNA revealed differences in IFN-gamma and IL-4 synthesis consistent with the hypothesis that Th2 T cells develop in young male SJL mice that regulate the relapsing phase of the disease. These data suggest that immunization of young male SJL mice with PLP 139-151 overrides a defect in antigen presentation responsible for the previously observed resistance to EAE, and that natural processing and presentation of neuroantigens during the course of acute EAE induces Th2 cells that prevent the relapse of disease.
...
PMID:Male SJL mice do not relapse after induction of EAE with PLP 139-151. 889 79

Regulation of experimental autoimmune encephalomyelitis (EAE) can be induced by anti-idiotype immunity against T cell receptor (TCR) fragments associated with major histocompatibility complex (MHC) molecules. However, we have recently found that preimmunization with an alpha-chain TCR CDR3 peptide (LYFCAARSNYQL) derived from myelin basic protein (MBP)-specific clones did not suppress but rather augmented the severity of EAE induced by MBP-specific T cells in SJL/J mice. To test whether CDR3 vaccination could control only a highly restricted T cell population, we studied the effect of the peptide against EAE induced by T cells specific for different Ag/MHC ligands and autoimmune diseases affecting non-neural tissues. In contrast to expectations, the peptide was found to augment not only EAE induced by MBP-specific T cells, but also proteolipid protein (PLP)-specific T cell- or PLP peptide-induced EAE in SJL/J mice, and MBP-induced EAE and adjuvant arthritis (AA) in rats. The CDR3 peptide was neither inhibitory nor supportive for Ag-induced activation of an encephalitogenic clone in vitro. In addition, the peptide treatment neither inhibited the induction of Ag-specific T cells nor altered the APC function of spleen cells. These findings, on the one hand, confirm previous results showing TCR peptide-induced enhancement of the disease and, on the other hand, indicate that the TCR CDR3 peptide may control T cells with broader Ag/MHC specificities than could be expected. Structural similarity among TCR idiotypes of autoimmune T cells may partly account for these results.
...
PMID:An alpha-chain TCR CDR3 peptide can enhance EAE induced by myelin basic protein or proteolipid protein. 889 82

Demyelinating diseases, such as multiple sclerosis (MS) in man or experimental allergic encephalomyelitis (EAE) in rodents, may include an associated immune response directed against myelin protein antigens such as the proteolipid protein (PLP) and the myelin basic protein (MBP). Development of an immune response has been attributed, in part, to the sequestration of central nervous system antigens behind the blood-brain barrier. Recently, we identified a novel gene, the golli gene, which overlaps the mbp gene. The Golli transcription unit produces a family of mRNAs, and their corresponding proteins possess MBP epitopes known to be encephalitogenic in EAE. Transcription of the golli gene was detected in immune system tissue. Therefore, we wished to determine whether genes that encode the two major myelin protein components, PLP and MBP, were expressed in the human thymus. Our data demonstrate that both the plp and golli genes are transcribed in the fetal human thymus. Moreover, both the PLP and DM-20 transcripts are produced from the plp gene, and the HOG 7 and HOG 5 transcripts are produced from the golli gene. Confocal fluorescent immunohistochemistry using antibodies for the PLP/DM-20 and Golli proteins, co-localized expression of these antigens to thymic macrophages. Thus, the plp and golli genes are expressed, and their corresponding protein produced, in an antigen presenting cell in the human immune system.
...
PMID:The major myelin protein genes are expressed in the human thymus. 889 93

Using experimental allergic encephalomyelitis, EAE, as a model for the study of autoimmune demyelinating disease in the CNS, previous studies have indicated that spread may occur with respect to the specificity of T cell responses during disease. This phenomenon, known as epitope spreading, is central to therapeutic strategies in multiple sclerosis (MS). However, in EAE, the clinical course, neuropathology and immunopathogenesis vary depending upon host factors and the method of disease induction. Since passive EAE in SJL/J mice resembles MS clinically and neuropathologically, this model was chosen to study the immune phenomenon of epitope spreading. T cells specific for whole 18.5 kDa MBP were used to initiate disease since MBP or one of its naturally occurring cleavage fragments may initiate a more physiological immune response than one generated to an artificially designed synthetic peptide. While a progressive increase in T cell responsiveness specific for the immunodominant MBP 87-106 region was observed during disease, there was no evidence of either intermolecular epitope spreading to the immunodominant region of proteolipid protein (PLP) 139-151 or of intramolecular epitope spreading to the exon 2 encoded region of MBP, which is spliced out of 18.5 kDa MBP. In addition there was no shift in immunodominance toward the subdominant MBP 16-35 region during disease. In contrast during active EAE induced by MBP, epitope spreading to the immunodominant epitope of PLP, 139-151, was observed. These data demonstrate that immune responses generated during passive versus active EAE may differ, and suggest that significant epitope spreading does not occur in chronic relapsing demyelinating disease initiated with T cells specific for whole MBP in the absence of exogenous antigen, complete Freund's adjuvant and pertussis. Implications of these findings with regard to epitope spreading in MS are discussed.
...
PMID:Epitope spreading occurs in active but not passive EAE induced by myelin basic protein. 889 18

The nature of the autoimmune T cell response to myelin oligodendrocyte glycoprotein (MOG), recently recognized as a potential target antigen in multiple sclerosis (MS), has not yet been characterized, in contrast to the T cell reactivity to other potential target antigens in MS such as myelin basic protein and proteolipid protein. Here, we show that the encephalitogenicity of the recombinant Ig-like domain of human MOG is associated, in H-2 b mice, with an immunodominant T cell reactivity against a single region of MOG spanning amino acids 35-55, accounting for the previously reported strong encephalitogenic activity of pMOG 35-55. A single injection of pMOG 35-55 with or without administration of pertussis toxin was sufficient to induce severe clinical experimental autoimmune encephalomyelitis (EAE) in H-2 b mice. Encephalitogenic pMOG 35-55-specific T cell lines derived from C3H.SW (V beta b) mice were diverse in their TCR V beta gene usage (V beta 1, V beta 6, V beta 8 and V beta 15), although V beta 8.2 was most predominantly expressed (48%). However, V beta 8 + T cells may only be part of the encephalitogenic MOG-specific T cell repertoire in H-2 b mice, as demonstrated by the susceptibility of C57L (V beta a) mice to disease induced by pMOG 35-55. Encephalitogenic T cell lines from V beta a mice were also diverse in their TCR V beta gene usage (V beta 1, V beta 2, V beta 6, V beta 14 and V beta 16). Such a heterogeneous TCT V beta gene expression by pMOG 35-55/I-A b-reactive T cells from both V beta a and V beta b H-2 b mice suggested multiple epitopes within pMOG 35-55. Analysis of the pattern of reactivity by pMOG 35-55-reactive T cells to a set of truncated peptides was not commensurate with independent nested epitopes, but revealed a requirement for recognition of a core sequence, YRSPFSRVV (pMOG 40-48). However, optimal stimulation was obtained with longer peptides, with each additional amino acid flanking either the N or the C terminus differentially increasing the stimulatory capacity of pMOG 40-48. Nonetheless, pMOG 40-48 was the minimal encephalitogenic epitope for both V beta a and V beta b mice. Thus, the T cell reactivity against the immunodominant encephalitogenic region of MOG is characterized by a diverse V beta gene usage and a requirement for the same core epitope. This pattern of reactivity may favor epitope-directed, rather than TCR-targeted, approaches to immunospecific therapy for MOG-related autoimmune disease.
...
PMID:Delineation of the minimal encephalitogenic epitope within the immunodominant region of myelin oligodendrocyte glycoprotein: diverse V beta gene usage by T cells recognizing the core epitope encephalitogenic for T cell receptor V beta b and T cell receptor V beta a H-2b mice. 889 62

Previous studies have shown golli-myelin basic protein (MBP) mRNA to be expressed in the thymus of normal SJL mice, but translation of the mRNA was not assessed. To test for the presence of immunoreactive protein, single cell suspensions were prepared from adult SJL thymus and cultured with syngeneic MBP-specific T cells. After 48 h [3H]thymidine was added to the microcultures to assess T cell proliferation. MBP-specific T cell lines proliferated strongly (stimulation index range, 13-31). T cell lines specific for MBP exon 2, MBP peptide 89-101, proteolipid protein peptide 139-151, and OVA gave stimulation indices of 10-13, 5-6, 2-3, and 2-3, respectively. Stimulatory activity could be abrogated by irradiation of either the thymic cells or the MBP-specific T cells. Stimulatory activity was a property of a minor population of plastic-adherent thymic cells. Monoclonal anti-I-As Ab added to the microcultures inhibited the reaction by 77%. MBP-specific T cells cultured with syngeneic nonirradiated thymus cells in the absence of added MBP transferred experimental autoimmune encephalomyelitis adoptively to syngeneic recipients. These findings indicate that golli-MBP mRNA is translated in normal SJL thymus, and that peptides reactive with MBP-specific T cells in the context of class II MHC molecules are expressed.
...
PMID:Thymic expression of myelin basic protein (MBP). Activation of MBP-specific T cells by thymic cells in the absence of exogenous MBP. 895 69

The present study sought to examine the immunopharmacologic effects of suramin on splenocytes from experimental allergic encephalomyelitis (EAE)-induced mice, taken in line with a previous observed action of suramin in ameliorating EAE. Suramin, a polysulfonated napthylurea, decreased the proliferation of T cells, in the presence of various stimuli, such as guinea pig myelin basic protein (MBP), mouse spinal cord homogenate (MSCH), bovine proteolipid protein (PLP), P1 (synthetic peptide 139-151 of PLP), and Mycobacterium tuberculosis (MTB). Suramin inhibited T cell proliferation in a dose-dependent manner. However, cytokine assays revealed that suramin increased antigen-induced levels of IL-4, whilst IFN-gamma levels were decreased. Using various doses of suramin (25, 15, and 5 micrograms/g), its cytokine modulatory effect displayed a consistent dose-dependent activity in vivo. This cytokine modulation commenced on week 2 after immunization and persisted all throughout the drug administration period, up to the 4th week. These results indicate that the prospects of using suramin in the treatment of multiple sclerosis may be feasible.
...
PMID:Suramin exerts in vivo cytokine modulatory properties on splenocytes from experimental allergic encephalomyelitis-induced SJL mice: implications for autoimmune disease therapy. 895 79

Multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS) characterized by primary demyelination, is believed to result from an autoimmune attack against myelin components. In view of their ability to induce experimental autoimmune encephalomyelitis (EAE), an animal model for MS, the quantitatively major malign proteins--myelin basic protein (MBP) and proteolipid protein (PLP)--have been extensively studied as the relevant primary antigens in MS, and therapeutic approaches have been targeted to counteract autoimmune reactivity to MBP and PLP. Accordingly, copolymer 1, a random synthetic amino acid copolymer crossreactive with MBP and highly protective against the induction of EAE with MBP or PLP, is not being extensively tested in clinical studies as a therapeutic agent for MS. However, increasing evidence suggests that autoimmune reactivity against other CNS-specific myelin proteins could also be involved in the pathogenesis of MS. In this context, we have demonstrated that peripheral blood lymphocytes from patients with MS respond predominantly to myelin oligodendrocyte glycoprotein (MOG) rather than to MBP or PLP, suggesting an important role for cell reactivity against MOG in the pathogenesis of MS. We have demonstrated that T-cell reactivity in MOG can also be pathogenic by inducing neurological disease in H-2u and H-2b mice with the same peptide of MOG, pMOG 35-55. Most interestingly, the expression of the disease differed with the different MHC backgrounds. Induction of a differentially expressed disease in different strains of mice with the same myelin antigen makes this new model particularly relevant to MS, where different expression of the disease is seen in different patients. Therefore, notwithstanding the importance of the autoimmune reactivity to MBP and PLP in MS, the potentially pathogenic autoimmune reactivity to MOG must now also be taken into consideration in therapeutic approaches to MS. In this context, we have investigated the possible effect of copolymer 1 treatment on autoimmune reactivity to MOG and on the development of EAE induced by MOG. Copolymer 1 was found to inhibit the binding of MOG peptides to MHC molecules, as well as the proliferation of MOG-reactive T cells, in a dose-dependent manner. In parallel, injection of copolymer 1 concomitantly with the encephalitogenic MOG peptide exerted a strong protective effect against the development of EAE. These preliminary data on the effect of copolymer 1 on the autoimmune response to MOG in mice indicate that copolymer 1 may also be effective in cases of MS where the autoimmune response to MOG prevails, and should therefore be further investigated in this context.
...
PMID:The autoimmune reactivity to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis is potentially pathogenic: effect of copolymer 1 on MOG-induced disease. 896 16

Copolymer 1 is a synthetic amino acid copolymer, effective in suppression of experimental allergic encephalomyelitis (EAE) induced in a variety of species. Copolymer 1 can suppress both acute and chronic relapsing EAE induced by either whole brain homogenate or the purified encephalitogens myelin basic protein (MBP) and proteolipid protein (PLP). Thus, the suppressive effect of copolymer 1 in EAE is a general phenomenon and is not restricted to a certain species, the disease type, or the encephalitogen used for EAE induction. The suppressive activity of copolymer 1 is, however, limited to EAE, and copolymer 1 has no nonspecific immunological activity. On the other hand, a marked degree of immunological cross-reactivity in both the cellular and humoral immune responses was demonstrated between MBP and copolymer 1. This cross-reactivity may be the underlying mechanism for the specific suppressive effect of copolymer 1 in EAE. In vivo and in vitro studies using both murine and human cell cultures suggest that the mechanism for copolymer 1 activity in EAE and multiple sclerosis involves, as an initial step, the binding of copolymer 1 to the major histocompatibility complex class II molecules on antigen-presenting cells. Following this step, two pathways may be activated: (1) induction of antigen-specific suppressor T cells by determinants shared between MBP and copolymer 1, or (2) competition with MBP and other myelin-associated antigens, PLP and myelin oligodendrocyte glycoprotein, for the activation of effector T cells. These two mechanisms can act either separately or in concert to interfere in the autoimmune processes that lead to the neurological damage in EAE and multiple sclerosis.
...
PMID:New insights into the mechanism of action of copolymer 1 in experimental allergic encephalomyelitis and multiple sclerosis. 896 19

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.
...
PMID:Prior exposure to superantigen can inhibit or exacerbate autoimmune encephalomyelitis: T-cell repertoire engaged by the autoantigen determines clinical outcome. 898 96

<< Previous 1 2 3 4 5 6 7 8 9 10