Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inflammatory infiltrate of the central nervous system in acute experimental allergic encephalomyelitis (EAE) in the guinea-pig has been isolated and characterized. Inflammatory cells found over the surface of the brain and spinal cord and within the leptomeninges have been isolated by washing, and were subsequently identified by a number of methods. By light microscopy approximately 60% were lymphocytes, 30% were cells of the mononuclear phagocyte series, and 5% were neutrophils: the occasional plasma cell and eosinophil were also identified. E, EA and EAC rosetting tests were used to determine the proportions of T lymphocytes (both early and late), and cells with Fc and C3 receptors respectively. Particular attention was paid to cells of the mononuclear phagocyte series bearing Fc and C3 receptors to determine whether any change or loss of these receptors was apparent. The percentage of phagocytic cells from the brain and spinal cord washes was also determined. Transmission and scanning electron microscopy showed that a large proportion of the inflammatory infiltrate consisted of cells of the mononuclear phagocyte series. This study therefore confirms that the cells of the mononuclear phagocyte series play a predominant role in EAE.
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PMID:Isolation and characterization of the inflammatory infiltrate in the central nervous system of the guinea-pig with experimental allergic encephalomyelitis. 696 81

Organ-specific autoimmune diseases and their animal models are characterized by the finding that the development of the diseases is closely associated with, or induced by, T cells reactive to organ-specific antigens. Therefore, the identification of T cell receptors (TCR) used by disease-inducing T cells within a short period of time is a key factor for designing TCR-based immunotherapy. The findings introduced in this article show that TCR associated with the development of multiple sclerosis and experimental autoimmune diseases including encephalomyelitis (EAE), neuritis (EAN) and carditis (EAC) are identifiable by complementarity-determining region 3 (CDR3) spectratyping analysis and subsequent sequencing of the CDR3 region of spectratype-derived TCR clones. It is also demonstrated that immunotherapy targeting disease-associated TCR using monoclonal antibodies and DNA vaccines significantly reduced the histological severity, and completely suppressed the inflammation in some animals. Since depletion or suppression of one of several types of effector cells does not significantly improve the severity of the disease, combined TCR-based immunotherapy should be considered as a primary therapy for T cell-mediated autoimmune diseases. TCR-based immunotherapy after rapid identification of autoimmune disease-associated TCR by CDR3 spectratyping can be applicable, not only to animal, but also to human autoimmune diseases whose pathomechanism is poorly understood.
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PMID:Characterization of T cell receptor (TCR) of organ-specific autoimmune disease-inducing T cells and TCR-based immunotherapy with DNA vaccines. 1102 29

Organ-specific autoimmune diseases are characterized by the presence of relapse and remittance of the clinical signs, and last for a long period of time in most cases without an appropriate treatment. Immunopathologically, T cells that respond to organ-specific autoantigens play an important role in the development of inflammatory lesions in the target organ. These pathogenic T cells that had been activated by various stimuli including preceding infection infiltrate the target organ in an antigen-specific manner and break the homeostasis of the organ. Furthermore, they secrete a large number of pro-inflammatory cytokines and chemokines, which recruit by-stander inflammatory cells in the lesion. Although general immunosuppressive drugs such as corticosteroid and cyclosporine are effective in suppressing clinical signs and inflammation, immunospecific therapy is essential for the establishment of long-lasting remission or complete cure. In order to achieve effective immunospecific therapy, several groups have focused on two key molecules that are deeply involved in pathogenesis of autoimmune diseases. One is the T cell receptor (TCR) expressed on pathogenic T cells and the other is the cytokine and chemokine receptor expressed in the target organ. Another important aspect of this issue is the reagent that is used for the suppression of the function of the key molecules. So far, monoclonal antibodies, peptide vaccines and DNA vaccines are the major reagents used for immunosuppressive therapies. In the present review, I introduce the results of immunotherapy obtained in my laboratory using TCR-based and chemokine receptor (chemoR)-based DNA in experimental autoimmune encephalomyelitis (EAE) and myocarditis (EAC) and discuss its effectiveness and pathomechanisms of immunosuppression. First, we administered DNA vaccines encoding pathogenic TCR Vbeta8.2, 10 (to Lewis rats) and 15 (to DA rats) and observed that these vaccinations protected animals from the development of EAE. Similar results were obtained in EAC. Second, DNAs encoding several chemoRs were prepared and administered after the challenge to neutralize the function of chemokines that are highly upregulated in the lesions. It was demonstrated that these chemoR DNAs suppress the relapse of chronic relapsing EAE and block the progression of EAC to dilated cardiomyopathy (manuscripts submitted for publication). These findings clearly indicate that DNA vaccination can be a powerful tool for treatment of organ-specific autoimmune diseases.
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PMID:New approach to immunotherapy against organ-specific autoimmune diseases with T cell receptor and chemokine receptor DNA vaccines. 1577 6

The extravasation of CD4(+) effector/memory T cells (TEM cells) across the blood-brain barrier (BBB) is a crucial step in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) or multiple sclerosis (MS). Endothelial ICAM-1 and ICAM-2 are essential for CD4(+) TEM cell crawling on the BBB prior to diapedesis. Here, we investigated the influence of cell surface levels of endothelial ICAM-1 in determining the cellular route of CD4(+) TEM -cell diapedesis across cytokine treated primary mouse BBB endothelial cells under physiological flow. Inflammatory conditions, inducing high levels of endothelial ICAM-1, promoted rapid initiation of transcellular diapedesis of CD4(+) T cells across the BBB, while intermediate levels of endothelial ICAM-1 favored paracellular CD4(+) T-cell diapedesis. Importantly, the route of T-cell diapedesis across the BBB was independent of loss of BBB barrier properties. Unexpectedly, a low number of CD4(+) TEM cells was found to cross the inflamed BBB in the absence of endothelial ICAM-1 and ICAM-2 via an obviously alternatively regulated transcellular pathway. In vivo, this translated to the development of ameliorated EAE in ICAM-1(null) //ICAM-2(-/-) C57BL/6J mice. Taken together, our study demonstrates that cell surface levels of endothelial ICAM-1 rather than the inflammatory stimulus or BBB integrity influence the pathway of T-cell diapedesis across the BBB.
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PMID:Cell surface levels of endothelial ICAM-1 influence the transcellular or paracellular T-cell diapedesis across the blood-brain barrier. 2554 37