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 explored antigenic differences between guinea pig (GP)-basic protein (BP), rat (Rt)-BP, and respective peptides from the encephalitogenic region for Lewis rats by comparing the fine specificity of T lymphocyte lines and clones selected from animals primed with these Ag. Encephalitogenic T cell lines specific for GP-BP or Rt-BP predictably recognized the corresponding 72-89 and to a lesser degree the 72-84 (S55S) amino acid sequence. T cell lines selected from rats primed with GP-S55S responded preferentially to GP-S55S compared to other peptides. A T cell line raised to Rt-S55S, however, initially recognized the S55S and S72-89 peptides but were nearly unresponsive to the intact GP-BP or Rt-BP. T cell clones selected from the Rt-S55S line at that point had two distinct patterns of response: clones that recognized both of the BP and the S55S peptides adoptively transferred delayed-type hypersensitivity and experimental autoimmune encephalomyelitis. These clones also recognized residues 69-81 (S67) but not peptide S75-89. In contrast, T cell clones that responded only to synthetic peptides GP-S55S and Rt-S55S but not to the parent BP adoptively transferred delayed-type hypersensitivity but not disease in Lewis rats. The same clones failed to respond to either the S67 or the S75-89 sequences. These results demonstrate that the encephalitogenic Rt-S55S sequence houses a minimum of two T cell epitopes with differing specificities and functions. One epitope is immuno-dominant and resembles the encephalitogenic region of the intact BP molecule. The second non-encephalitogenic epitope is restricted to the S55S sequences and is not shared by the parent BP, the S67, or the S75-89 sequences. Both types of Rt-S55S-specific clones differ in fine specificity from encephalitogenic clones selected from GP-BP immunized rats, thus indicating that uniformity of T cell recognition of the encephalitogenic epitope is not an absolute condition for T cells to be encephalitogenic.
J Immunol 1988 Dec 01
PMID:Encephalitogenic T cell clones with variant receptor specificity. 246 May 51

Immunizing Lewis rats with guinea pig myelin basic protein (MBP) yielded an encephalitogen specific, Ia-restricted, rat-mouse T cell hybridoma 5.10, which was used to establish a clonotypic mAb (10.18) that binds to and precipitates the rat TCR. By two-dimensional gel electrophoresis, the rat TCR was shown to consist of two disulfide-linked peptide chains with mol wt of 48,000 and 39,000. 10.18 binds the majority of cells in MBP-specific T cell lines that are capable of transferring experimental allergic encephalomyelitis (EAE) to Lewis rat recipients, but does not bind to either a purified protein derivative of tuberculin-specific cell line or an OVA-specific line. Furthermore, soluble 10.18 can block antigen-specific stimulation of hybridoma 5.10 but cannot control hybridomas, while immobilized 10.18 stimulates 5.10, but cannot control the hybrids. Though 10.18+ cells are very rare in normal rats, increase of 10.18+ cells is observed in MBP-primed paralyzed rats. Finally, when 10.18 is injected into MBP-primed Lewis rats, EAE is abrogated. We have thus characterized EAE as a "mono-idiotypic" autoimmune disease.
J Exp Med 1988 Dec 01
PMID:Protection from experimental allergic encephalomyelitis conferred by a monoclonal antibody directed against a shared idiotype on rat T cell receptors specific for myelin basic protein. 246 7

Cop 1 is a synthetic basic random copolymer of L-alanine, L-glutamic acid, L-lysine, and L-tyrosine in a residue molar ratio of 6.0:1.9:4.7:1.0 and with a molecular weight of 21,000 which proved to be effective in specific suppression of experimental allergic encephalomyelitis and has been proposed as a candidate drug against multiple sclerosis. In the present study we further investigated the mechanism of Cop 1 suppressive activity and tested whether Cop 1 could inhibit the specific T-cell response to myelin basic protein (BP). Eight BP-specific T-cell lines and clones with various H-2 restrictions and antigenic specificities were used. The responses of all these lines and clones to BP, as followed by both cell proliferation and interleukin 2 secretion assays, were affected by Cop 1. For one line, a direct cross proliferation with Cop 1 was observed, whereas in the other seven lines and clones, Cop 1 specifically inhibited the responses to BP in a competitive dose-dependent manner. The inhibition of the response to BP is specific to Cop 1, as D-Cop 1 and another random acidic polymer, poly(Tyr,Glu,Ala) (TGA), both of which were previously demonstrated to be ineffective in suppression of experimental allergic encephalomyelitis, did not inhibit the response to BP. Furthermore, Cop 1 specifically inhibited only the response of the T-cell lines and clones to BP. It did not inhibit their response to the mitogen Con A, nor did it inhibit the responses of the purified protein derivative-specific T-cell line and clone. These results suggest that Cop 1 may be effective in suppression of experimental allergic encephalomyelitis, not only because of the selective stimulation of suppressor T cells, as we have previously demonstrated, but also by specific inhibition of BP-specific effector T cells.
Proc Natl Acad Sci U S A 1988 Dec
PMID:Specific inhibition of the T-cell response to myelin basic protein by the synthetic copolymer Cop 1. 246 52

A chronic remitting-relapsing form of experimental allergic encephalomyelitis (EAE) has been produced in monkeys sensitized to homologous myelin basic protein in Freund's complete adjuvants by the technique of suboptimal treatment after the onset of disease. Not only does the clinical course resemble that of human multiple sclerosis more closely than does the clinical course of acute EAE, but so also does the histological reaction, with more-nearly pure demyelination, rather than the hyperacute hemorrhagic-necrotic lesions that occur so commonly in untreated monkeys with ordinary acute EAE.
Ann Neurol 1988 Dec
PMID:Chronic remitting-relapsing experimental allergic encephalomyelitis induced in monkeys with homologous myelin basic protein. 246 50

The central nervous system (CNS) contains several types of neuroglial cells. In the present study, we characterized different types of glial cells in rat CNS by using single and combined immuno- and enzyme-histochemical methods, and immunofluorescence techniques. Two recently developed monoclonal antibodies (mAbs) against rat macrophages-associated antigens appeared to recognize a subpopulation of glial cells in the CNS of normal adult rats. These ED4- and ED8-positive glial cells were predominantly located in the white matter of adult rat CNS and shared morphological features with microglia. ED4 and ED8 were applied in a double staining combined with mAbs and an antiserum raised against galactocerebroside (GalC) to identify oligodendrocytes, or with anti-glial fibrillary acidic protein antiserum (GFA) to identify astrocytes. We also used a mAb against myelin basic protein (MBP) to identify oligodendrocytes. It appeared that ED4 and ED8 recognized a subpopulation of oligodendrocytes. MAbs against GalC and MBP recognized cells in an immunoperoxidase staining with a morphology identical to that of the ED8-positive cells and part of the ED4-positive cells. Frozen sections of Lewis rats CNS with acute experimental allergic encephalomyelitis (EAE) were investigated, where infiltrating brain macrophages could be found which stained positively with ED4 and ED8 as well as with the monocyte/macrophage mAbs ED1 and ED2. These brain macrophages did not stain when GalC, MBP and GFA markers were applied. Furthermore, ED4+GalC+ and ED8+GalC+ oligodendrocytes were present in the CNS white matter of EAE animals with similar appearance as in normal adult rats. With the currently used markers, we could not detect a third type of neuroglial cell, besides the astrocytes and oligodendrocytes. Thus, none of our anti-macrophage monoclonals recognized the presumptive microglia. Only under pathological conditions, e.g., in inflammatory infiltrates in the course of EAE, could brain macrophages be detected in the CNS parenchyma and only in the direct vicinity of blood vessels, indicating their hematogenous origin.
Immunobiology 1988 Dec
PMID:Discrimination between different types of neuroglial cells in rat central nervous system using combined immuno- and enzyme-histochemical methods. 246 92

The effect of timing of a local host-versus-graft reaction on the induction of acute experimental allergic encephalomyelitis (EAE) was studied in guinea pigs. 20 x 10(7) gamma-irradiated allogeneic cells injected 4 days after encephalitogenic challenge resulted in the development of EAE with an earlier onset, an increased delayed-type hypersensitivity (DTH) response and an increase in lymphoid cell infiltration in the spinal cord. Challenge with allogeneic cells on days -4 and -7, however, produced a delay in onset and a protracted course of disease, with 30-40% of the animals recovering. Evidence of disease was confirmed histologically.
J Neuroimmunol 1989 Dec
PMID:Modulation of experimental allergic encephalomyelitis by a host-versus-graft reaction: a clinicopathological study. 247 57

Histological studies were performed on Lewis rats with experimental allergic encephalomyelitis (EAE) passively transferred by myelin basic protein (MBP)-sensitized syngeneic spleen cells in order to determine the relationship between demyelination and neurological signs. Neither inflammation nor demyelination was present on the day prior to the onset of neurological signs but both were present in the spinal roots and spinal cord on the day of onset of tail weakness (4 days after passive transfer). Demyelination and the neurological signs both increased over the next 48 h. There was evidence that the caudal roots were more severely affected than the rostral roots. The peripheral nerves were spared. Demyelination in the spinal cord was concentrated in the dorsal root entry and ventral root exit zones. The initial stages of repair of demyelinated spinal root fibres by Schwann cells were observed on the earliest day that clinical recovery commenced (day 7). At this time some demyelinated fibres were closely associated with debris-free Schwann cells, and occasional fibres were completely invested by 1-2 layers of Schwann cell cytoplasm. Remyelination (compact myelin lamellae formation) by Schwann cells was first observed in the spinal roots on day 9. By the time of complete clinical recovery (day 11) the majority of affected spinal root cores had thin new myelin sheaths. Repair of central nervous system myelin by oligodendrocytes was slower than peripheral nervous system myelin repair. Investment of demyelinated spinal cord axons by oligodendrocytes was observed on day 9, and remyelination by these cells was seen on day 10. We conclude that the neurological signs of passively induced MBP-EAE can be accounted for by demyelination of the lumbar, sacral and coccygeal spinal roots and spinal cord root entry and exit zones, and that the subsequent clinical recovery can be explained by investment and remyelination of demyelinated peripheral and central nervous system fibres by Schwann cells and oligodendrocytes respectively.
J Neuroimmunol 1989 Dec
PMID:Demyelination and early remyelination in experimental allergic encephalomyelitis passively transferred with myelin basic protein-sensitized lymphocytes in the Lewis rat. 247 58

T cell lines to myelin basic protein (MBP) developed following in vitro culture cause experimental allergic encephalomyelitis (EAE) upon transfer into naive recipient mice. We have, however, repeatedly observed that MBP-specific T cell lines lose their ability to transfer EAE after 40 days in culture. Analyses of such cell lines failed to show any differences in their proliferative responses to antigen, or in the secretion of interleukin-2 (IL-2) and/or IL-4 when compared to their encephalitogenic counterparts. In contrast, examinations of T cell receptor (TCR) beta-chain gene rearrangement patterns showed sequential changes in the clonal population of cells concomitant with the loss of encephalitogenic function. Furthermore, transfer of a non-encephalitogenic, genotypically altered cell line after long-term in vitro culture into mice challenged with MBP suppressed the development of EAE. These findings suggest that the development of such putative regulatory cells in vivo may be involved in the recovery in EAE.
J Neuroimmunol 1989 Dec
PMID:Spontaneous development in vitro of a myelin basic protein-specific suppressor T cell line. 247 59

Lymphocytes from the central nervous system (CNS) of animals with acute experimental autoimmune encephalomyelitis (EAE) have been isolated and characterized. The lymphocytes were separated from Lewis rats which were injected either with an emulsion of myelin basic protein (BP) emulsified in complete Freund's adjuvant (CFA) to cause EAE or with CFA alone as a control. Using density gradient centrifugation, from 9 days post-inoculation (d.p.i.) (before clinical signs appear), to 19 d.p.i. (after signs abate), lymphocytes were recovered from the spinal cords and popliteal lymph nodes of BP-injected animals. Lymphocyte cell number, phenotype, and antigen specificity were determined. Results show that the onset of clinical signs correlated with lymphocyte influx into the CNS. A clinical index of 1 was associated with less than 10(6) cells per gram of CNS wet weight (cells/g CNS) while animals with a clinical index of 4 had more than 15 X 10(6) cells/g CNS. During remission, when only minor residual neurologic signs were evident, significant numbers of lymphocytes (greater than 10(7) cells/g CNS) could still be isolated. In contrast, no lymphocytes were obtained from control CNS tissue. The phenotype of the recovered cells was predominantly of the helper/inducer T cell subset (greater than 40%). Although the percentages of these cells in the CNS were increased when compared to the lymph nodes, I-A expression on CNS-isolated lymphocytes showed the most significant increase with disease progression. Recovered lymphocytes responded to both BP and CFA-related antigens indicating that both CNS-specific and CNS-non-specific inflammatory cells were present in the exudate.
J Neuroimmunol 1989 Dec
PMID:Experimental autoimmune encephalomyelitis: isolation and characterization of inflammatory cells from the central nervous system. 247 60

Due to critical amino acid changes in the 72-89 sequence, the determinant of human (Hu) basic protein (BP) that induces experimental autoimmune encephalomyelitis (EAE) in Lewis rats most likely differs from rat and guinea pig BP. To discern encephalitogenic sequence(s), the immunodominant epitopes recognized by Hu-BP-specific T cell lines were identified using synthetic peptides that corresponded to the Hu-BP sequence. The Hu-BP-reactive T cell line contained two distinct specificities, one directed at the 87-99 (Hu) sequence restricted by I-E, and the second directed at the 55-74 (Hu) sequence restricted by I-A. T cells specific for the 87-99 determinant recognized both Hu- and Rt-BP, were highly encephalitogenic, and accounted for the experimental autoimmune encephalomyelitis-inducing activity of the Hu-BP line. T cells directed at the S55-74 (Hu) sequence did not recognize Rt-BP and were not encephalitogenic. The same TCR V genes (homologous to the mouse V alpha 2 and V beta 8 families) that we showed previously were utilized preferentially in response to the I-A restricted 72-89 encephalitogenic sequence were also present in T cell lines specific for both the S55-74 and S87-99 epitopes. These data indicate that encephalitogenic activity of BP in Lewis rats is related to discrete T cell epitopes that are present on or cross-react with rat-BP. Furthermore it would appear that genes in the TCR V alpha 2 and V beta 8 families are widely used in response to different BP epitopes restricted by either I-A or I-E molecules.
J Immunol 1989 Dec 01
PMID:Determinants of human myelin basic protein that induce encephalitogenic T cells in Lewis rats. 247 81


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