Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis and their application for new therapeutic strategies.
The etiology of multiple sclerosis (MS), a demyelinating disorder of the central nervous system (CNS), is not yet known. Immunological, clinical and pathological studies suggest, however, that T lymphocytes directed against myelin antigens are involved in the pathogenesis of MS. The examination of an experimental animal model for MS, experimental allergic encephalomyelitis (EAE), demonstrated that myelin basic protein-(MBP) or proteolipidprotein-(PLP) specific T cells mediate the destruction of CNS myelin. In recent years, elegant studies in EAE showed that encephalitogenic T cells recognize short peptides of MBP or PLP in the context of MHC/HLA-class II molecules, express a restricted number of T cell receptor (TCR) molecules and secrete interferon-gamma and tumor necrosis factor-alpha/beta. Understanding the pathogenetic steps of demyelination at the molecular level led to highly specific immunotherapies of EAE targeting each individual molecule. MBP- and PLP-specific T cells with similar properties could also be isolated from MS patients and control individuals. Due to their heterogeneity in terms of specificity, function and TCR usage, it was difficult, however, to draw definite conclusions from these results, so far. The recent approval of interferon-beta, a cytokine that antagonizes a number of the effects of interferon-gamma, for the treatment of MS has raised great interest in examining novel strategies for immunotherapies in MS. The basic concepts as well as the current candidates for such new immunotherapies will be outlined in this brief article.
Martin
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Department of Neurology, University of Tübingen Medical School, Federal Republic of Germany.
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D016899:Interferon-beta / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D008285:Major Histocompatibility Complex; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009185:Myelin Proteins / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014612:Vaccines
D008233:Lymphotoxin-alpha; D009185:Myelin Proteins; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines; D016899:Interferon-beta; D007371:Interferon-gamma