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)

Measles is associated with alterations in immune regulation that sometimes lead to secondary infections or autoimmune encephalomyelitis. Simultaneously, an effective measles virus-specific immune response develops. To relate immune activation to measles and its complications, we studied the spontaneous proliferation of blood mononuclear cells and circulating levels of soluble interleukin-2 receptor and CD8 T-cell antigens in 126 patients with complicated or uncomplicated measles at various stages of the disease. Spontaneous proliferation of mononuclear cells, which was present through the first week of the rash, was greater in cells from patients with measles (8787 +/- 1403 cpm) than in those from healthy children (1529 +/- 237 cpm, P less than 0.0001). Levels of soluble interleukin-2 receptor (3385 +/- 195 units per milliliter) and CD8 (4145 +/- 437 units per milliliter) were higher in patients with measles than in those with other infectious diseases (2377 +/- 440, P = 0.003; 2399 +/- 771, P = 0.0374) or in healthy children (865 +/- 138, P less than 0.0001; 1026 +/- 169, P less than 0.0001). Levels of soluble interleukin-2 receptor were elevated before the onset of the rash and remained elevated for several weeks. In contrast, levels of soluble CD8 increased only when the rash appeared, and subsided quickly. Spontaneous proliferation of mononuclear cells and levels of soluble CD8 were similar in patients with uncomplicated disease, pneumonia, or encephalomyelitis, but soluble interleukin-2 receptor levels were lower in patients with encephalomyelitis (2312 +/- 314 vs. 3455 +/- 247 units per milliliter in uncomplicated measles; P = 0.01). In patients with encephalomyelitis, cerebrospinal fluid levels of soluble CD8 (686 +/- 350 units per milliliter), but not interleukin-2 receptor (9 +/- 8.3 units per milliliter), were increased. We conclude that the proliferative phase of the immune response, as measured by the release of soluble interleukin-2 receptor, begins before the rash appears, continues for several weeks in those without complications, but does not occur within the nervous system. In contrast, the effector phase of the immune response, as measured by the release of soluble CD8, coincides with the appearance and disappearance of the rash and occurs within the nervous system during encephalomyelitis.
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PMID:Immune activation in measles. 249 61

Infection of BALB/c mice with the M variant of encephalomyocarditis virus resulted in the development of a paralytic syndrome in 7 to 10 days. The paralysis was maximal during the period of viral clearance; most of the animals recovered from the initial deficit and showed no delayed recurrences. Pathologically, the white matter of brain and spinal cord showed well-demarcated areas of perivascular cuffing, demyelination, and, during recovery, remyelination by oligodendrocytes--all suggestive of postinfectious encephalomyelitis. Depletion of either the CD4 or CD8 subset of T cells in vivo with the appropriate monoclonal antibody, GK1.5 or 2.43, respectively, administered one day (24 h) prior to infection was sufficient to limit the development of the paralytic syndrome by 79% (GK1.5) and 82% (2.43).
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PMID:Treatment of encephalomyocarditis virus-induced central nervous system demyelination with monoclonal anti-T-cell antibodies. 255 Jun 66

The production and characterization of an anti-guinea pig B cell monoclonal antibody is described. Immunocytochemical techniques using this antibody and others recognizing a Pan T cell antigen and T cell subsets were employed to study frozen sections of spinal cord from guinea pigs with chronic relapsing experimental allergic encephalomyelitis. T and B cells were found in both perivascular lesions and the central nervous system parenchyma, with the major T cell infiltration occurring by the end of the acute phase of disease. The distribution of T cell subsets suggests a phenotypic selectivity in favour of the transport of CT6 (putative CD8)+ve cells across the blood-brain barrier.
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PMID:A quantitative immunocytochemical study of the infiltrating lymphocytes in the spinal cord of guinea pigs with chronic relapsing experimental allergic encephalomyelitis. 258 95

The oligodendrocyte (Od), a glial cell that produces myelin in the central nervous system, may be a target for autoreactive T cells in autoimmune demyelinating processes, although not expressing major histocompatibility complex (MHC) products. To analyze Od-T-cell interactions, we selected from normal SJL/J mouse splenocytes sensitized in vitro by Lewis rat Od a T-cell clone, named C2, exhibiting a surface phenotype of mature T cell (Thy 1+, CD3+, CD8+, CD4-, asialo-GM1-). C2 T cells displayed a specific cytotoxicity to syngeneic Od as well as to rat Od, but not to astrocytes or lymphoblasts, or to YAC-1 cells, a target for natural killer and lymphokine-activated killer activity. The T-cell receptor of clone C2 was found to be a CD3-associated alpha/beta-chain heterodimer similar to that usually expressed by antigen-specific MHC-restricted mature T cells. Attempts to block the C2-mediated cytolysis by a series of monoclonal antibodies showed that both the CD3-T-cell receptor complex and the CD8 accessory molecule were required for OD-T-cell interaction and confirmed the lack of involvement of polymorphic MHC products as epitope-presenting structures. Antibodies directed against a surface Od glycoprotein, previously shown to elicit demyelinating autoantibodies in experimental autoimmune encephalomyelitis, fully blocked the cytotoxicity of T-cell clone C2 to its Od target. These data suggest that an epitope of a surface Od glycoprotein may be directly and specifically recognized and killed by autoreactive T cells expressing an alpha/beta receptor without conventional MHC restriction.
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PMID:Oligodendrocyte-specific autoreactive T cells using an alpha/beta T-cell receptor kill their target without self restriction. 278 60

Albino Oxford (AO) rats in comparison to the Dark August (DA) strain exhibit lower susceptibility to the induction of experimental autoimmune encephalomyelitis (EAE), and interleukin 2 (IL-2) production by their spleen and lymph node cells is significantly lower. The cellular analysis of these differences in the outcome of the EAE induction, possibly related to the differences in the IL-2 production, revealed different changes in the T cell subsets in the draining lymph node (DLN) and different cellular composition of the mononuclear infiltrates in the central nervous system (CNS). After the encephalitogenic challenge, the frequency of CD8+ T cells was much higher and the expansion of CD4+ T cells was much lower in the DLN of "low" IL-2 producer rats. AO rats have not shown any clinical sign of EAE, although histological lesions in the early phases of EAE (Day 7-9) were similar to those seen in diseased DA rats. CD4/CD8 T cell ratios and the number of cells bearing receptor for IL-2 (IL-2-R+ cells) and cells bearing class II MHC antigens (Ia+) were significantly lower in the mononuclear cell infiltrates of AO rats. These data are compatible with the notion that CD4+ IL-2-R+ encephalitogenic T cells induce clinical signs of EAE in susceptible animals and show that CD8+ T cells are present in a higher percentage in the lesions of the symptom-free AO rats.
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PMID:Experimental autoimmune encephalomyelitis in "low" and "high" interleukin 2 producer rats. I. Cellular basis of induction. 278 57

In this study, pretreatment of Lewis rats with a syngeneic encephalitogenic T cell line (S1) was found to be able to constantly induce resistance to the subsequent induction of transferred experimental autoimmune encephalomyelitis (tEAE). This treatment was capable of protecting recipient animals for at least 2-4 months. Here we show an enhanced suppressor T(anti-S1) cell activity, which can be readily detected in the lymphoid organs of animals which recovered from S1-induced tEAE, or from rats pretreated with attenuated (irradiated, fixative treated or water-lysed) S1 cells. Anti-S1 cells, which uniformly express the CD8 phenotype, were selectively stimulated to grow and expand into lines by confronting primed lymphoid cells with irradiated S1 cells in culture. The proliferative response of anti-S1 cells was independent of myelin basic protein and antigen-presenting cells, and the responses against unrelated encephalitogenic T cell lines were minimal. It was also found that none of the monoclonal antibodies tested (including CD8 and MHC class I antigen-specific antibodies) was able to block S1/anti-S1 interactions. These cells are functionally suppressive to the proliferation of S1 cells in vitro, are specifically cytolytic directed against the EAE-inducing S1 cells and are able to antagonize encephalitogenic capacity of S1 cells in vivo. In vivo elimination of the CD8+ T subset from Lewis rats, using a combined treatment of thymectomy and OX-8 antibody injection before the initial cell transfer, totally blocked the induction of resistance. Our experiments document that induction of functionally active suppressor T cells is responsible for the induced resistance observed in tEAE.
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PMID:Regulatory circuits in autoimmunity: recruitment of counter-regulatory CD8+ T cells by encephalitogenic CD4+ T line cells. 290 95

Down-regulatory phenomena have been described in several experimental models of tissue-specific, T-cell-mediated autoimmunity. For example, resistance to active induction of experimental autoimmune encephalomyelitis (EAE) can be induced by pretreating animals with non-pathogenic inocula of autoantigen or effector cells. Moreover, animals that have recovered from one EAE episode are resistant to subsequent induction of EAE. In some models, resistance to EAE has been transferred with immune cells to naive recipients. These experiments, which were based on transfers of unseparated immune cell populations, are difficult to interpret. Immune suppression circuits are known to be complex and involve various distinct cellular subsets. To further complicate the issue, resistance to EAE can be transferred not only by suppressor cells, but also by encephalitogenic effector cells injected in 'subclinical' doses. We describe now the isolation of homogeneous T lymphocyte lines from the spleens of Lewis rats that had recovered from T-cell-mediated EAE (tEAE) caused by the MBP-specific T cell line S1. These spleen-derived T line cells express the CD8 phenotype and specifically respond to determinants on the inducing S1 line, but not to the autoantigen MBP. Furthermore, the anti-S1 cells selectively lyse the encephalitogenic S1 T line in vitro and efficiently neutralize their encephalitogenic capacity in vivo.
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PMID:Suppression of experimentally induced autoimmune encephalomyelitis by cytolytic T-T cell interactions. 296 94

Immunological parameters in rhesus monkeys, resistant and susceptible to experimental allergic encephalomyelitis (EAE), were studied. Monkeys immunized with complete Freund's adjuvant (CFA) alone and EAE resistant monkeys immunized with a low dose of bovine brain homogenate emulsified in CFA did not show significant fluctuations in numbers of granulocytes, lymphocytes and lymphocyte subsets (CD4; CD8; GM13, a subset of CD8) and anti-brain homogenate antibody titres remained low. EAE susceptible monkeys immunized with a high dose of myelin developed EAE significantly faster than monkeys immunized with a low dose of brain homogenate. During the induction phase all EAE susceptible monkeys, in contrast to the CFA controls and EAE resistant monkeys, showed an increase in the numbers of granulocytes and the CD4/CD8 ratios and had high antibody titres specific for the immunizing antigens. The most significant disease-related changes were observed after the onset of clinical signs. These included a granulocytosis, a lymphopenia and a decrease in the CD4/CD8 ratio, indicating a selective loss of CD4+ lymphocytes. A major difference between monkeys immunized with myelin and brain homogenate was the significant increase in the percentage of GM13+ lymphocytes after the onset of clinical signs in the latter group. Increases in the CD4/CD8 ratio and antibody titres during the induction phase may be prognostic factors for the subsequent development of EAE.
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PMID:Experimental allergic encephalomyelitis in rhesus monkeys: I. Immunological parameters in EAE resistant and susceptible rhesus monkeys. 365 11

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a relevant mouse model of multiple sclerosis. Demyelination is linked to persistent TMEV infection of the central nervous system and characterized by perivascular inflammatory mononuclear infiltrates and primary demyelination. Our previous results have shown that susceptibility correlates with the temporal development of chronic virus-specific delayed-type hypersensitivity (DTH) responses and suggest that inflammatory processes mediated by T cells specific for an immunodominant determinant on virus capsid protein 2 (VP2(74-86)) play a major immunopathologic role in SJL/J mice. In this study we have further defined the T cell-dependent nature and specificity of the demyelinating process in susceptible SJL/J mice by showing that thymectomized irradiated bone marrow-restored mice fail to develop chronic demyelination and that i.v. adoptive transfer of polyclonal TMEV-specific T cells before intracerebral infection with a suboptimal dose of the BeAn strain of TMEV led to increased incidence and accelerated onset of clinical disease. The data also show that demyelination is dependent on the activity of virus-specific CD4+ T cells because in vivo depletion with anti-CD4, but not anti-CD8, mAb led to significantly diminished incidence and severity of demyelination concomitant with a decrease in TMEV-specific DTH reactivity. In addition, the adoptive transfer of a TMEV-specific, DTH-mediating CD4+ I-A(s)-restricted Th1 line (sTV1) specific for the immunodominant VP2(74-86) epitope also led to increased incidence and accelerated onset of clinical disease only in TMEV-infected recipients. Collectively, the results of this and the companion paper demonstrate the highly significant immunopathologic contribution of CD4+ T cell responses specific for an immunodominant viral epitope to the chronic central nervous system demyelination observed in TMEV-infected SJL/J mice.
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PMID:Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. VI. Potentiation of demyelination with and characterization of an immunopathologic CD4+ T cell line specific for an immunodominant VP2 epitope. 750 40

We have previously shown that orally administered myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis in both the Lewis rat and the SJL mouse. In the Lewis rat fed low doses of MBP, we found that protection can be adoptively transferred by CD8+ cells and that these cells inhibit immune responses via the secretion of TGF-beta after Ag-specific triggering. In the present study, we investigated the cellular requirements for the generation of active suppression following oral administration of MBP in SJL and (PLJ x SJL)F1 mice. We first determined the frequency of MBP cells secreting Th1 (IFN-gamma) and Th2 (IL-4/IL-10) cytokines or TGF-beta after oral administration of MBP. We found that in SJL mice, orally administered MBP (0.5 mg/feeding) led to an increased frequency of TGF-beta-, IL-4-, and IL-10-secreting cells and a decreased frequency of IFN-gamma-producing cells. This pattern was observed in both CD4+ and CD8+ populations; adoptive transfer of either CD4+ or CD8+ cells from orally tolerized mice suppressed autoimmune encephalomyelitis in recipient animals. We then studied the role of CD8+ cells on the generation of oral tolerance to MBP by depleting CD8+ cells in vivo with anti-CD8 mAb. Oral tolerance was successfully induced in such animals, as demonstrated by a decrease in clinical disease and T cell proliferative responses, although there was less TGF-beta production in vitro and less disease protection on days 20 to 22 in CD8-depleted animals. These studies demonstrate that CD4+ cells in the absence of CD8+ cells can mediate the active suppression component of oral tolerance in mice and that there is a reciprocal relationship between Th1- and Th2-type cytokine production associated with oral tolerization.
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PMID:Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediate active suppression. 754 26


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