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)

Alkyllysophospholipids are synthetic analogues of natural phospholipids possessing a high immunomodulating and antitumoral capacity. Experimental autoimmune encephalomyelitis is a model disease for multiple sclerosis which can be induced by injecting rats with myelin basic protein, MBP. The effect of one alkyllysophospholipid, ET-18-OCH3, on the course of experimental autoimmune encephalomyelitis was investigated. It was found that animals treated with ET-18-OCH3 showed only weak signs of disease. MBP specific T-cell lines were co-cultivated with ET-18-OCH3. The compound suppressed T-cell proliferation markedly, suggesting that this might be its mode of action in vivo. Since ET-18-OCH3 has only low toxicity in man, it could be of interest to perform further studies on its effects on autoimmune, demyelinating disease.
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PMID:Alkyllysophospholipid prevents induction of experimental allergic encephalomyelitis. 137 62

The efficacy of antigen-specific immunoregulation as a treatment for the efferent limb of an autoimmune disease was tested in a rat model of adoptive experimental autoimmune encephalomyelitis (EAE). Lewis rats receiving 4-5 x 10(7) guinea pig (GP) myelin basic protein (MBP)-activated lymph node T cell blasts from GPMBP/CFA sensitized donors routinely show clinical signs of disease 5-6 days post transfer. Intravenous injection of GPMBP coupled to syngeneic splenocytes using the chemical cross-linker carbodiimide was effective in completely abrogating the expression of clinical EAE in rats that received MBP-specific T cells 2 days previously. Partial inhibition was also observed in rats injected as early as day 0 (the same day as MBP-specific T cell transfer) and as late as 1 day prior to the onset of clinical signs (days 4-5 post transfer). Unresponsiveness was shown to be dose-dependent, dependent on the route of injection of the neuroantigen-coupled splenocytes, and was antigen-specific. Splenocytes coupled with GP or rat MBP (which are identical within the major encephalitogenic GP68-86 Lewis rat determinant with the exception of the residue at position 80) were equally efficient at eliminating disease expression in recipients of GPMBP-specific T cells. In contrast, splenocytes coupled with bovine or rabbit MBP (which differ significantly from GPMBP within the 68-86 region) had no inhibitory effect. The antigen specificity of the tolerance induction was also illustrated by the fact that splenocytes coupled with GP68-86, but not those coupled with the truncated GP68-84 peptide, induced profound unresponsiveness. Interestingly, de novo antigen processing by the antigen-coupled cells did not appear to be necessary as the inclusion of antigen processing inhibitors had no effect on inhibition of disease. However, the use of the carbodiimide coupling reagent was critical for the induction of unresponsiveness as essentially equivalent amounts of 125I-labelled MBP were bound in its presence or absence, but only splenocytes incubated in the presence of both MBP and carbodiimide inhibited clinical expression of disease. Antigen-specific tolerance is thus an effective means of inhibiting expression of clinical disease in the rat EAE model, and a powerful tool for determining the fine epitope specificity of encephalitogenic T cells.
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PMID:Antigen-specific inhibition of the adoptive transfer of experimental autoimmune encephalomyelitis in Lewis rats. 137 53

A synthetic peptide corresponding to residues 87-99 (S87-99) of myelin basic protein (BP) induced the proliferation of an encephalitogenic, BP-specific T cell line selected in vitro from inbred Buffalo-strain rats (RT1b). Active immunization with guinea pig (GP)-BP or S87-99 in complete Freund's adjuvant (CFA) and intravenous pertussigen induced acute experimental autoimmune encephalomyelitis (EAE) 10-12 days after immunization. Fifty percent of recovered rats developed a single relapse 17-21 days after immunization. T lymphocytes selected in vitro with S87-99 transferred acute, non-relapsing EAE into naive recipients. Histological examination during acute EAE revealed foci of inflammatory cells associated with demyelination in the spinal cords and peripheral nerve roots. Thus, as in several other rodent strains, the 87-99 region of BP is antigenic and encephalitogenic in the inbred Buffalo-strain rat. Additionally, the 87-99 sequence of GP-BP was predicted to be antigenic by two different methods. These results suggest that the 87-99 region of BP, which is highly conserved among mammalian species, may be widely encephalitogenic due to antigen-intrinsic properties.
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PMID:The synthetic 87-99 peptide of myelin basic protein is encephalitogenic in Buffalo rats. 137 54

Using experimental autoimmune encephalomyelitis (EAE) in the rat as a model of central nervous system (CNS) inflammation, activated and quiescent T lymphocytes with different antigen specificities were labelled with the fluorescent dye Hoechst 33342 and tested by fluorescence microscopy for their ability to accumulate in different regions of the spinal cord and in other organs at varying times post inoculation. With this highly sensitive assay it was found that activated myelin basic protein (MBP)-specific T cell lines accumulated in the spinal cord (a 1000-fold increase in the lumbar/sacral region by day 4) and caused clinical signs of EAE. In contrast, interleukin-2 (IL-2)-maintained (quiescent) MBP-specific T cell lines failed to accumulate in the CNS and cause disease. Activated ovalbumin (OA)-specific and purified protein derivative of tuberculin (PPD)-specific T cell lines were also found at significantly higher levels in the spinal cord than non-activated cells although they failed to accumulate to a substantial degree when injected alone. When injected with activated MBP-specific T cells the activated OA- and PPD-specific cell lines accumulated in the spinal cord following initial accumulation of the MBP-specific cells, demonstrating that during the inflammatory process there is considerable non-specific recruitment of cells into the inflammatory site. CNS accumulation of activated MBP-specific T cell lines occurred 1-2 days later in irradiated animals than in non-irradiated recipients. This was consistent with irradiated animals also exhibiting a later onset of disease and suggests that irradiation may directly affect the endothelium in a way that makes it less adhesive. In conclusion, this study demonstrates that activated lymphocytes of any specificity enter the spinal cord, and that the neuro-antigen specific cells accumulate there and lead to the recruitment of other cells. Non-activated cells, even those with neural antigen specificity fail to enter the cord. Understanding the nature of what an 'activated' lymphocyte is may allow us to design strategies to inhibit such immune-mediated inflammation.
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PMID:Selective localisation of neuro-specific T lymphocytes in the central nervous system. 137 55

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] and related analogs have been shown to exert immunoinhibitory effects on activated lymphocytes in vitro. However, the effects of the hormone on the mammalian immune response in vivo have not been well studied. To examine the possible immunoactions of 1,25-(OH)2D3 in vivo, we employed a murine model of experimental autoimmune encephalomyelitis (EAE). In this model, T helper lymphocyte clones developed from lines of lymphocytes reactive to myelin basic protein (MBP) confer MBP immunoreactivity and demyelinating central nervous system disease on syngeneic, naive recipients of the T cell clone. Similar to peripheral blood mononuclear cells incubated with mitogen, the T cell clone evaluated in this study expressed a high-affinity specific receptor for 1,25-(OH)2D3 (VDR; K(in) = 0.03 nM) upon exposure to MBP. The MBP-stimulated clone elicited a ninefold enhancement of the local delayed hypersensitivity (DTH) response when as few as 0.5 x 10(5) cells of the T cell clone were injected into the foot pad of recipient mice. The DTH response in the recipient was completely blocked when the clone was preincubated with greater than or equal to 10(-8) M 1,25-(OH)2D3 before transfer; the half-maximal inhibitory concentration of hormone (EC50) was 5 x 10(-9) M. These data indicate that exposure of antigen-reactive T helper lymphocytes to a VDR saturating concentration of 1,25-(OH)2D3 can dramatically lessen the expression of immunoreactivity in vivo.
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PMID:1,25-Dihydroxyvitamin D3 inhibits the passive transfer of cellular immunity by a myelin basic protein-specific T cell clone. 137 30

Ag-specific tolerance induced by the i.v. administration of splenocytes coupled with mouse spinal cord homogenate, containing a mixture of myelin Ag, dramatically inhibits development and expression of clinical and histologic signs of both active and adoptive forms of relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL/J host. Here we examined the dose-dependency, route of tolerogen administration, and fine neuroantigen specificity of inhibition of adoptive R-EAE. Expression of clinical R-EAE induced by a polyclonal population of bovine myelin basic protein (MBP)-specific effector T cells was dramatically inhibited in a dose-dependent manner following the i.v., but not s.c. or i.p., injection of MBP-coupled splenocytes. The exquisite Ag specificity of the inhibition was evident by the observation that splenocytes coupled with intact bovine MBP or species variants of MBP homologous with bovine MBP within the major encephalitogenic region (amino acids 84-104), but not with proteolipid protein or mouse kidney homogenate, were able to suppress disease expression. Splenocytes coupled with the MBP84-104 peptide, containing a nested set of the major SJL/J encephalitogenic epitopes, completely inhibited peptide-specific T cell responses, but only partially inhibited the expression of disease transferred by T cells specific for intact MBP, suggesting the participation of T cell responses specific for additional MBP determinants in disease pathogenesis. However, splenocytes coupled with previously identified minor SJL/J encephalitogenic epitopes (MBP91-104 or MBP17-27), or with the Lewis rat major encephalitogenic epitope (MBP68-86), did not suppress disease expression. Collectively, the results demonstrate that MBP84-104-specific T cells and T cells specific for an as yet unidentified MBP epitope(s) contribute to the pathology of R-EAE. In addition, the results demonstrate that peptide-specific tolerance induction appears to have potential for the treatment of T cell-mediated inflammatory diseases.
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PMID:Regulation of the effector stages of experimental autoimmune encephalomyelitis via neuroantigen-specific tolerance induction. II. Fine specificity of effector T cell inhibition. 137 98

T cell sensitization to two myelin components, myelin basic protein (MBP) and myelin proteolipid protein (PLP), may be important to the pathogenesis of multiple sclerosis (MS). Using the limiting dilution assay, we demonstrated that the blood of MS patients had an increased frequency of MBP-reactive T cells compared with normal subjects and patients with other neurological diseases (OND) and rheumatoid arthritis. There was no difference in T cell frequency to a synthetic peptide, PLP139-151, or Herpes simplex virus. Within cerebrospinal fluid (CSF), 37% of IL-2/IL-4-reactive T cell isolates from MS patients responded either to MBP or PLP139-151 while only 5% of similar isolates from OND patients responded to these myelin antigens. The mean relative frequency of MBP-reactive T cells within CSF from MS patients was significantly higher than that of OND patients (22 x 10(-5) cells versus 1 x 10(-5) cells) and was similar to that of MBP reactive T cells within the central nervous system of rats with experimental autoimmune encephalomyelitis. These results lend new support to the hypothesis that myelin-reactive T cells mediate disease in MS.
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PMID:Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis. 137 22

The course of experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis, is affected by immunoregulatory T lymphocytes. When animals are immunized with encephalitogenic peptide of myelin basic protein and recover from the first episode of EAE, they become resistant to a second induction of this disease. Animals depleted of CD8+ T cells by antibody-mediated clearance were used to examine the role of CD8+ T cells in EAE. These cells were found to be major participants in the resistance to a second induction of EAE but were not essential for spontaneous recovery from the first episode of the disease.
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PMID:Role of CD8+ T cells in murine experimental allergic encephalomyelitis. 137 98

In order to assess the role of idiotype (Id) and the anti-Id network in murine experimental autoimmune encephalomyelitis (EAE), Id-bearing monoclonal antibodies (mAb) to human myelin basic protein (MBP) peptide acetyl 1-9, as well as mAb anti-Id, were developed in EAE-susceptible PL/J mice (H-2u). These mice recognize MBP residues acetyl 1-9 as an encephalitogenic determinant. Reactivities of PL/J Id-bearing mAbs to MBP and to MBP peptides were identical to those of mAbs generated against the same MBP peptide in EAE-resistant BALB/c mice (H-2d), even though isotypes of the mAbs differed. By using an inhibitory ELISA and immunoblotting, it was demonstrated that one PL/J mAb anti-Id recognized a public or framework Id, whereas another PL/J mAb-anti Id was directed to a private Id more restricted to the paratopic site. Two Id-bearing PL/J mAbs shared a cross-reactive Id (IdX) on the light chain, and an interstrain IdX was present on both the heavy and light chains of mAbs raised in PL/J and BALB/c mice to the same MBP peptide. The PL/J mAb anti-Id was capable of cross-regulating the production of Id-bearing mAbs by hybridomas across murine strains. These findings suggest that a restrictive family of germ-line genes encode for these Id-bearing antibodies to MBP peptide, irrespective of whether the MBP peptide is encephalitogenic in the murine strain immunized. Manipulation of the Id network may provide a means for modifying autoimmune demyelinating diseases of the central nervous system.
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PMID:Interstrain cross-reactive idiotypes on monoclonal antibodies to an encephalitogenic myelin basic protein peptide. 137 43

Proteolipid protein (PLP) is a major component of the central nervous system (CNS) myelin membrane and has been shown to induce acute experimental autoimmune encephalomyelitis (EAE) in genetically susceptible animals. Here we describe conditions by which a relapsing-remitting form of EAE can be reliably induced in SJL/J mice either actively immunized with the major encephalitogenic PLP peptide, PLP13-151(S), or following adoptive transfer of PLP139-151(S)-specific T cells. The disease follows a reliable relapsing-remitting course with acute clinical signs first appearing 6-20 days after priming or transfer and relapses first appearing at 30-45 days. The initial onset of disease correlates with delayed-type hypersensitivity (DTH) reactivity specific for PLP139-151(S), in the apparent absence of T cell reactivity to the major myelin basic protein (MBP) peptide. Histologically, both the active and adoptive forms of the disease are characterized by extensive mononuclear cell infiltration and severe demyelination of the CNS. These results suggest that T cell responses specific for PLP139-151(S) are sufficient to induce clinical and histological R-EAE in SJL/J mice. This model should prove useful for examination of the cellular and molecular events involved in clinical relapses and perhaps in determining the role of PLP-specific T cell responses in multiple sclerosis (MS).
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PMID:Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein. 137 28


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