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)

The effectiveness and the mechanism of T cell vaccination were studied in two experimental models of autoimmune disease. The attempt to modulate autoimmune disease via idiotypic regulation of autoreactive antigen-specific T cells was first shown in the rat experimental autoimmune encephalomyelitis (EAE) model where inactivated EAE-inducing T cells could both immunize and protect rats from EAE. We previously reported that low dose T cell vaccination against EAE in Lewis rats was immunologically specific, long lasting and extremely efficient in preventing adoptive transfer of the disease. In experimental autoimmune uveitis (EAU) T cell vaccination was also found to be effective. In both cases, antigen or mitogen activation of the T cells prior to inoculation was required. In the EAE model, T cell vaccination appeared to be associated with two sets of T lymphocytes (CD4+ CD8- helper and CD4- CD8+ cytotoxic/suppressor cells) which were cloned and found to be specifically reactive to the vaccine cells. These anti-idiotypic T cell clones were able to antagonistically modulate the in vitro proliferation of encephalitogenic Z1a cells. In vivo, transfer of the lymph node cells (from which the anti-idiotypic clones were derived) from vaccinated animals to naive syngeneic recipients conferred resistance to EAE. In the EAU model, we also found a consistent immunological response raised against different activated T cells (four T cell lines with irrelevant specificities and mitogen-activated lymphoid cells) in addition to the anti-idiotypic cells. This response, apparently directed to T cell activation markers, might combine with the anti-idiotypic response to regulate autoimmunity.
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PMID:T cell vaccination in autoimmune diseases. 179 4

Administration of the immunosuppressive agent, SK&F 105685, has demonstrated immunosuppressive activity in several animal models of autoimmunity such as adjuvant arthritis and experimental autoimmune encephalomyelitis. The mechanism of action of SK&F 105685 in these autoimmune disease models appears to be the induction of non-specific suppressor cells (SC) detected in the spleen and bone marrow of treated animals. In this study we have examined the kinetics of SC appearance in the spleen and bone marrow following treatment with 30 mg/kg/day, p.o., for 1-6 days. SC activity was apparent following a single dose and increased with successive treatments. Treatment with SK&F 105685 also resulted in significantly enhanced myelopoiesis as measured by a 128% increase in the frequency of bone marrow myeloid progenitors (CFU-GM). Mechanistic studies indicated that in vitro treatment of bone marrow stromal cell cultures with SK&F 105685 upregulated the production of colony stimulating activity (CSA) detectable in a rat CFU-GM assay. Further, in vitro studies revealed that the SC in the bone marrow or spleens of SK&F 105685-treated rats admixed with normal marrow cells inhibited CFU-GM formation at a six-fold less cell concentration than cells obtained from control rats. These in vitro results suggest that the SK&F 105685-induced myelopoiesis is regulated by the subsequent generation of SC.
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PMID:Induction of non-specific suppressor cells and myeloregulatory effects of an immunomodulatory azaspirane, SK&F 105685. 182 31

Paraneoplastic neurological syndromes are of two types: some are more often seen without than with cancers and may therefore be called "occasionally para neoplastic" (e.g. chronic sensorimotor polyneuropathy and polymyositis), while others are fairly regularly associated with cancers, and particularly with small cell lung carcinoma. In this category falls subacute encephalomyelitis, an entity of broad anatomico-clinical spectrum including limbic encephalitis and subacute sensory neuronopathy; the patient's serum and cerebrospinal fluid may contain neuronal antinuclear antibodies. One type of subacute cerebellar degeneration is characterized by the presence of antibodies specifically directed against Purkinje cell cytoplasmic antigens, and it is associated with ovarian and mammary cancers. The other type shows no antibodies or different antibodies and sometimes neuronal antinuclear antibodies; the latter case may represent the cerebellar form of subacute encephalopathy. Because it may be either a true autoimmune disease or a true paraneoplastic syndrome, Lambert-Eaton myasthenic syndrome, caused by autoantibodies that block the voltage-dependent calcium channels, stands out as the most convincing argument in support of the autoimmune paraneoplastic syndrome theory. The theory, which refers to cross-antigenicity, cannot be extended to the other syndromes without reservation: there is no evidence that autoantibodies are neurotoxic, and specific autoantibodies in high levels are sometimes detected in patients with cancer but without any neurological symptom. Nevertheless, the finding of circulating antineuronal antibodies in patients with a suggestive clinical syndrome should prompt investigations for cancer perhaps at an early stage.
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PMID:[Paraneoplastic neurologic syndromes]. 182 23

The immunopathogenesis of MS is discussed in the light of data recently obtained in Experimental Autoimmune Encephalomyelitis (EAE), a myelin specific experimental autoimmune disease reflecting the first, inflammatory phase of MS plaque generation. EAE is caused by CD4+ T cells specific for defined myelin protein, like MBP and PLP. In rats and mice there is a marked dominance of the autoantigenic peptide epitopes on the one hand, and the T cell receptor V regions on the other. During T cell mediated EAE, clonotypically counterregulatory CD8+ T cells are induced, which specifically neutralize the encephalitogenic T clones.
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PMID:Immunopathogenesis of multiple sclerosis. 189 86

The immunomodulatory azaspirane SK&F 105685 has immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of SK&F 105685 appears to be the induction of nonspecific suppressor cell (SC) activity. SC appear to be "null cells," that is, cells that lack specific cell surface markers of mature B cells, T cells, natural killer (NK) cells, or macrophages. Because we hypothesized that the induction of SC was associated with enhanced hematopoiesis, we sought to determine the hematopoietic potential of SK&F 105685. Recombinant interleukin 1 alpha (rIL-1) was included as a positive control for hematopoietic stimulation in our studies. We demonstrate here that administration of SK&F 105685 increases the number of granulocyte-macrophage colony-forming units (CFU-GM) within the bone marrow 24 h after injection in a dose-dependent manner. In addition, the percentage of CFU-GM in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity (CSA) present in the serum of treated animals. In our experiments IL-1 did not increase marrow CFU-GM; however, splenic CFU-GM, the proportion of CFU-GM in S-phase of the cell cycle, and serum CSA were all increased 24 h after a single treatment. Administration of SK&F 105685 24 h prior to lethal irradiation resulted in a dose-related increase in the number of surviving mice. These results demonstrate that SK&F 105685 and rIL-1 stimulate myelopoiesis in vivo and suggest a mechanism by which prophylactic treatment with these agents protects mice from otherwise lethal irradiation.
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PMID:Administration of an immunomodulatory azaspirane, SK&F 105685, or human recombinant interleukin 1 stimulates myelopoiesis and enhances survival from lethal irradiation in C57Bl/6 mice. 189 48

A series of analogue peptides have been generated, using as a template the core region of the OVA 323-339 peptide identified as critical in determining binding to I-Ad. Several of these "core extended" peptides had increased affinities for the I-Ad molecule compared to the native sequence, and were able to inhibit activation of an I-Ad-restricted T cell hybridoma in vitro. The induction of a T cell proliferative response to a peptide antigen could be inhibited by co-administration of core-extended peptide with antigen in the same adjuvant emulsion. Furthermore, inhibition also occurred when the inhibitor molecule was delivered separately one day before immunization. Finally, the induction of the autoimmune disease, experimental allergic encephalomyelitis (EAE), in susceptible mice could be reduced by the administration of a core-extended peptide with high affinity for the appropriate class II molecule. These findings have implications for the use of MHC antagonists in the control and treatment of MHC-associated autoimmune conditions in humans.
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PMID:Inhibition of antigen presentation in vitro and in vivo by MHC antagonist peptides. 196 93

Retinal S-antigen is widely used to study the LEW rat model of experimental autoimmune uveoretinitis (EAU). In this report, we have examined the T cell receptor V gene usage of several T cell lines recognizing either pathogenic or nonpathogenic sites on S-antigen to determine whether the V alpha 510 and V beta 510 rat homologues of the murine V alpha 2 and V beta 8 families, respectively, are used by uveitogenic T cells. Using cDNA probes for a LEW rat T cell receptor specific for the encephalitogenic determinant of myelin basic protein, we have found that in the retinal S-antigen/EAU model for autoimmune disease, pathogenicity correlates with usage of those rat V genes. Thus, all of the pathogenic lines were found to express T cell receptors of the V beta 510 and V alpha 510 families; conversely, V beta 510 usage was not detected in any of the nonpathogenic lines. Usage of these V regions has been associated with pathogenicity in the murine and rat models of experimental autoimmune encephalomyelitis, and now with S-antigen-induced EAU.
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PMID:Conserved T cell receptor V gene usage by uveitogenic T cells. 198 68

Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute to the inflammatory response associated with autoimmune diseases. Transforming growth factor beta 1 (TGF-beta 1) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown that microgram amounts of TGF-beta 1, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) and relapsing experimental allergic encephalomyelitis (REAE), the animal models for rheumatoid arthritis and multiple sclerosis, respectively. When administered during induction of the disease, TGF-beta 1 prevents CIA but only delays the onset of REAE by 2-3 days. However, when administered during a remission. TGF-beta 1 prevents the occurrence of relapses in REAE. The results suggest that TGF-beta 1 has powerful anti-inflammatory effects, mimicking in some respects the beneficial effects of immunosuppressive drugs in these experimental models of autoimmune disease, but without discernable adverse effects.
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PMID:Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. 201

The effect of the anti-tumour agent alkyl-lysophospholipid (ALP) ET-18-OCH3 on the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the mouse was investigated. Experimental allergic encephalomyelitis developed in the majority (greater than 96%) of mice immunized with autologous spinal cord homogenate in Freund's complete adjuvant. Alkyl-lysophospholipid, in doses of 25 mg/kg/day or 50 mg/kg/day, inhibited the onset of clinical signs of acute phase CREAE when orally administered starting on the day of disease induction. Similarly if treatment with 50 mg/kg/day was delayed until day 9 post-inoculation the incidence of disease and severity of clinical signs were also significantly reduced (P less than 0.02) as compared with vehicle fed animals. However, when treatment began on day 12, just prior to the onset of clinical disease, although the incidence of disease was not significantly altered the severity of disease was significantly (P less than 0.002) reduced compared with vehicle treated animals. These data suggest that although the major effect of ALP is on the inhibition of the generation of the autoimmune response there appeared to be some therapeutic benefit at a later stage of acute disease. Therefore, this study was extended to the treatment of post-acute phase remission animals. It was found that the oral administration of 50 mg/kg/day marginally reduced and that 75 mg/kg/day significantly (P less than 0.05) reduced the incidence of relapsing disease compared with vehicle treated controls. This suggests that ET-18-OCH3 may have some potential in the treatment of ongoing autoimmune disease of the central nervous system.
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PMID:Inhibition of chronic relapsing experimental allergic encephalomyelitis in the mouse by the alkyl-lysophospholipid ET-18-OCH3. 205 Apr 42

Nonobese diabetic (NOD) mice spontaneously develop a T-cell-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in humans. T-cell clones that specifically recognize pancreatic islet cell antigens can be derived from NOD mice, and most of these have been diabetogenic upon transfer to healthy recipients. We report herein the sequences of the T-cell receptor alpha and beta chains from four NOD-derived, islet-specific clones. The sequences are quite heterogeneous--in the junctional regions, specifically--so there seems to be little hope for treating this disease with specific anti-T-cell receptor reagents. This result contrasts with the strikingly restricted junctional region sequences reported for the receptors on clones derived from mice with experimental allergic encephalomyelitis, another T-cell-mediated autoimmune disease. We discuss possible explanations for this difference.
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PMID:Islet-specific T-cell clones from nonobese diabetic mice express heterogeneous T-cell receptors. 206 98


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