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)

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats and some strains of mice is typically a monophasic disease, and recovered animals are resistant to reinduction of disease. We demonstrate that SJL mice remain susceptible to disease after recovery, and suffer a second episode of disease when reinjected with spinal cord homogenate in complete Freund's adjuvant. Reinduced disease occurs earlier after injection than the initial disease (mean onset 7.3 days compared with 14.5 days), and has comparable severity and incidence. The susceptibility to reinduced disease is present for at least 20 weeks after the initial injection. If the initial episode of EAE is elicited using a synthetic peptide of proteolipid protein, then reinjection of the same peptide causes reinduced disease. PL/J mice and PL/J x SJL F1 mice are also susceptible to reinduced disease which occurs with an accelerated onset and higher incidence than the initial disease. We conclude that SJL and PL/J mice have a defect in immunoregulation which causes them to be susceptible to recurrent episodes of autoimmune disease.
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PMID:Reinduction of experimental autoimmune encephalomyelitis in mice. 753 49

To compare effects of insulin-like growth factor I (IGF-I) and placebo treatment on lesions that resemble those seen during active demyelination in multiple sclerosis, we induced experimental autoimmune encephalomyelitis in Lewis rats with an emulsion containing guinea pig spinal cord and Freund's adjuvant. On day 12-13, pairs of rats with the same degree of weakness were given either IGF-I or placebo intravenously twice daily for 8 days. After 8 days of placebo or IGF-I (200 micrograms/day or 1 mg/day) treatment, the spinal cord lesions were studied by in situ hybridization and with immunocytochemical and morphological methods. IGF-I produced significant reductions in numbers and areas of demyelinating lesions. These lesions contained axons surrounded by regenerating myelin segments instead of demyelinated axons seen in the placebo-treated rats. Relative mRNA levels for myelin basic protein, proteolipid protein (PLP), and 2',3'-cyclic nucleotide 3'-phosphodiesterase in lesions of IGF-I-treated rats were significantly higher than they were in placebo-treated rats. PLP mRNA-containing oligodendroglia also were more numerous and relative PLP mRNA levels per oligodendrocyte were higher in lesions of IGF-I-treated rats. Finally, a significantly higher proportion of proliferating cells were oligodendroglia-like cells in lesions of IGF-I-treated rats. We think that IGF-I effects on oligodendrocytes, myelin protein synthesis, and myelin regeneration reduced lesion severity and promoted clinical recovery in this experimental autoimmune encephalomyelitis model. These IGF-I actions may also benefit patients with multiple sclerosis.
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PMID:Insulin-like growth factor I treatment reduces demyelination and up-regulates gene expression of myelin-related proteins in experimental autoimmune encephalomyelitis. 754 Nov 43

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease induced by immunization with myelin basic protein (MBP), proteolipid protein, or encephalitogenic peptides from these myelin components. EAE resembles basic protein multiple sclerosis in some of its clinical and histologic features, and serves as an experimental model for this and other autoimmune diseases. In this study, we examine i.v. peptide therapy of EAE in detail, and show that repeated i.v. injections of MBP peptides effectively treat EAE in (PLJxSJL)F1 mice. In this study, administration of the immunodominant epitope (MBP Ac1-11) prevents MBP-induced disease, whereas the subdominant epitope MBP 31-47 is neither required nor sufficient. Intravenous administration of substituted MBP peptide analogues is also effective in treating EAE, provided the peptide side chains presumed to be involved in TCR contact and MHC binding are preserved. A substituted MBP peptide analogue that forms long-lived peptide-MHC complexes in vivo is more effective than the unmodified MBP peptide. Lower doses of the substituted peptide analogue are effective, and the effect is longer lasting than treatment with the unmodified peptide. Clinical signs of EAE are reversed by injection of the substituted peptide during the acute phase of disease. Moreover, treatment of mice in the remission phase of EAE results in a dramatically reduced incidence of relapse. In summary, we have shown that EAE can be reversed after onset and treated during remission with an MBP peptide analogue that has been modified for improved therapeutic potency.
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PMID:Reversal of acute experimental autoimmune encephalomyelitis and prevention of relapses by treatment with a myelin basic protein peptide analogue modified to form long-lived peptide-MHC complexes. 754 83

We compared the T cell responses of Lewis (LEW) and DA rats to guinea pig myelin basic protein (MBP), the synthetic peptides corresponding to the epitopes that are encephalitogenic in the LEW strain (MBP73-86, MBP68-86, and MBP87-99), and bovine proteolipid protein (PLP). DA and LEW rats were susceptible to experimental autoimmune encephalomyelitis (EAE) induced with MBP or MBP68-86, but the peptide was less active in DA rats than in intact MBP molecule. MBP73-86 and MBP87-99 induced EAE in LEW rats but not in the DA strain. MBP89-169 was also encephalitogenic in DA rats. Encephalitogenic CDa+ T cell lines and clones derived from MBP-sensitized DA rats secreted IFN-gamma and TNF-alpha and proliferated to MBP and MBP89-169, but not to MBP68-88. However, T cells from MBP68-86-sensitized DA or LEW rats proliferated specifically in an I-A-restricted response to MBP68-86. T cells from MBP87-99-immunized LEW rats responded to MBP87-99 in the context of I-E, whereas the peptide-specific response of MBP87-99 immunized DA rats was I-A-restricted, although FACScan analysis indicated that DA rats express both I-A and I-E. DA rats were also highly susceptible to EAE induced with PLP; 0.6 nmol was Encephalitogenic for DA rats, but did not induce clinical EAE in LEW rats. Although both DA and LEW rats are highly susceptible to EAE, we demonstrate marked differences in the array of myelin epitopes capable of inducing the disease, as well as the MHC restriction of these epitopes, between the two rat strains.
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PMID:A comparative study of experimental autoimmune encephalomyelitis in Lewis and DA rats. 754 85

Experimental autoimmune encephalomyelitis (EAE) was induced in the Lewis rat by the passive transfer of a cytotoxic CD4+ T cell clone specific for the 72-89 peptide of guinea-pig myelin basic protein (MBP). Histological studies on rats with neurological signs showed that inflammation was present in the proximal peripheral nervous system (PNS), namely the spinal roots, as well as in the central nervous system (CNS). The main sites of demyelination were the spinal roots in the PNS, and the spinal cord root entry and exit zones in the CNS. The major involvement of the proximal PNS in autoimmune disease directed at MBP is in marked contrast to EAE induced by immunisation with myelin proteolipid protein, where the inflammation and demyelination are restricted to the CNS. These findings may have implications for the human inflammatory demyelinating diseases including multiple sclerosis, in which MBP is a putative target antigen.
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PMID:The proximal peripheral nervous system is a major site of demyelination in experimental autoimmune encephalomyelitis induced in the Lewis rat by a myelin basic protein-specific T cell clone. 754 59

In experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, we have previously shown that the disease is mediated by Th1 cells, which recognize tryptophan 144 as the primary TCR contact point. Here we describe an altered peptide ligand (APL), generated by a single amino acid substitution (tryptophan to glutamine) at position 144 (Q144), which inhibits the development of EAE induced with the native PLP 139-151 peptide (W144). We show that the APL induces T cells that are cross-reactive with the native peptide and that these cells produce Th2 (IL-4 and IL-10) and Th0 (IFN gamma and IL-10) cytokines. Adoptive transfer of T cell lines generated with the APL confer protection from EAE. These data show that changing a single amino acid in an antigenic peptide can significantly influence T cell differentiation and suggest that immune deviation may be one of the mechanisms by which APLs can inhibit an autoimmune disease.
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PMID:An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. 758 31

A predominant response to myelin oligodendrocyte glycoprotein (MOG) was recently observed in patients with multiple sclerosis (MS). To study the possible pathogenic role of T cell response to MOG in MS, we have investigated the encephalitogenic potential of MOG. Synthetic MOG peptides, pMOG 1-21, 35-55, 67-87, 104-117 and 202-218, representing predicted T cell epitopes, were injected into C57BL/6J and C3H.SW (H-2b) mice. The mice developed significant specific T cell responses to pMOG 1-21, pMOG 35-55 and pMOG 104-117. However, pMOG 35-55 was the only MOG peptide which could induce neurological impairment. The highly reproducible disease was chronic, with ascending paralysis and neuropathology comparable with those observed in experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein or proteolipid protein, except that in H-2b mice the disease was consistently non-remitting. These features differ markedly from those which we recently observed in PL (H-2u) mice with pMOG 35-55-induced disease. In PL mice, pMOG 35-55-induces atypical chronic relapsing EAE, the expression and progression of which are unpredictable. Hence, in different mouse strains, the same MOG peptide can induce typical EAE characterized by ascending paralysis, or atypical EAE with unpredictable clinical signs. pMOG 35-55-specific T cells from H-2b mice recognized an epitope within amino acids 40-55 of the MOG molecule, and pMOG 40-55-reactive T cell lines were encephalitogenic upon transfer into syngeneic recipients. The encephalitogenic pMOG 35-55-reactive C57BL/6J T cell lines expressed V beta 1, V beta 6, V beta 8, V beta 14 and V beta 15 gene segments, and the pMOG 35-55-reactive C3H.SW T cell lines expressed V beta 1, V beta 2, V beta 6, V beta 8, V beta 10, V beta 14, and V beta 15 gene segments. However, in both mouse strains, the utilization of the V beta 8 gene product was predominant (40-43%). The highly reproducible encephalitogenic activity of pMOG 35-55 strongly suggests a pathogenic role for T cell reactivity to MOG in MS and supports the possibility that MOG may also be a primary target antigen in the disease.
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PMID:A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H-2b mice: fine specificity and T cell receptor V beta expression of encephalitogenic T cells. 762 71

Viral infections have been associated with the initiation and exacerbations often observed with autoimmune disease. Mechanisms by which viruses may play a role in the development of autoreactive immune responses include polyclonal activation of B and T cells, molecular mimicry, viral infection of immune cells, exposure of sequestered antigens, or altered host cell expression (neoantigen or altered self) in virus infected host cells. We have been studying the immune response generated to self proteins in association with viral infection. Here we evaluate the effects of viral infection on the development of an autoimmune disease of the central nervous system, experimental allergic encephalomyelitis. A vaccinia virus construct, VVplp was made containing the coding region for rat myelin proteolipid protein (PLP). Cells infected with VVplp were found to express PLP protein in vitro. Central nervous system disease was not detectable in mice vaccinated with VVplp. However, mice vaccinated with VVplp and later challenged with encephalitogenic peptides derived from PLP were found to have enhanced disease with earlier onset of symptoms when compared to mice treated with a control vaccinia virus construct. This enhancement of disease was found to peak at 10 days post challenge with the encephalitogenic PLP peptide. Clinical disease and an inflammatory response in the central nervous system was evident in mice previously vaccinated with VVplp but not in control vaccinated mice at this time. These results indicate that prior infection with a virus capable of coding for self protein can predispose the host to an accentuated autoimmune response.
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PMID:Enhancement of autoimmune disease using recombinant vaccinia virus encoding myelin proteolipid protein. 769 50

We have derived a panel of CD4+, TCR-alpha/beta + T cell clones from SJL (H-2s) mice specific for an encephalitogenic determinant of myelin proteolipid protein (PLP) 139-151 (HSLGKWLGHPDKF). All the clones are Ag specific and IAs restricted, but they show heterogeneity in their ability to induce experimental allergic encephalomyelitis (EAE), i.e., one group induces EAE in naive mice, a second group induces disease only in mice that are pretreated with pertussis and irradiation, whereas a third group is essentially nonencephalitogenic. To determine the basis for this functional heterogeneity, the clones were tested for the expression of adhesion molecules and cytokines and for Ag-specific cytolytic activity. All of the clones expressed comparable levels of LFA-1 and CD44 but lacked expression of Mel 14. However, those clones that induced EAE only in irradiation- and pertussis-treated recipients did not express VLA4. Because pretreatment with pertussis has been suggested to increase permeability of the blood-brain barrier and facilitate migration of T cells into the central nervous system, the absence of VLA4 on this group of clones may account for the need for pretreatment to induce EAE. The nonencephalitogenic clones expressed all of the adhesion molecules tested but were not cytolytic in vitro and failed to produce one or more of the proinflammatory cytokines after Ag-specific stimulation. One nonencephalitogenic clone that did not produce many cytokines on activation with specific Ag, however, could be activated with Con A to express mRNA for most cytokines and this was accompanied by a concomitant change in the encephalitogenic potency of this clone. These results suggest that adhesion molecules and cytokines both play a critical role in the encephalitogenicity of PLP peptide-specific T cell clones. Furthermore, the nonencephalitogenicity of some clones may be related to a defect in Ag-mediated activation.
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PMID:Cytokines and adhesion molecules contribute to the ability of myelin proteolipid protein-specific T cell clones to mediate experimental allergic encephalomyelitis. 769 46

The lymphokine production of two T-cell clones, which both recognize epitopes within the encephalitogenic 139-151 sequence of myelin proteolipid protein, was examined after stimulation with immobilized antibodies to the CD3 moiety of the T-cell-receptor complex. Clone A1 produced interleukin (IL)-2 and interferon (IFN)-gamma, but no IL-4, while clone D5 produced IL-4, but no IL-2 or IFN-gamma. A1 therefore belongs to the T-helper type 1 (Th1) subset, while D5 is a Th2 clone. In addition, the Th1 clone induced severe experimental allergic encephalomyelitis (EAE), while the Th2 clone did not induce any signs of EAE. Synthetic peptides were used to demonstrate that these clones recognized slightly different epitopes within the 139-151 sequence. Histidine 139 was shown to be optimal for the stimulation of the Th2 clone, while the presence of this residue inhibited the stimulation of the Th1 clone. Th2 cells specific for an encephalitogenic peptide may be important in the regulation of encephalitogenic Th1 cells.
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PMID:Fine-specificity differences in the recognition of an encephalitogenic peptide by T helper 1 and 2 cells. 769 54


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