Impairment of TNF-Receptor-1 Signaling but not Fas Signaling Diminishes T-Cell Apoptosis in Myelin Oligodendrocyte Glycoprotein Peptide-Induced Chronic Demyelinating Autoimmune Encephalomyelitis in Mice |
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Authors: | Rosilla Bachmann Hans-Pietro Eugster Karl Frei Adriano Fontana and Hans Lassmann |
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Institution: | Institute of Neurology, University of Vienna, Schwarzspanierstrasse 17,1090 Wien, Austria. |
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Abstract: | T-cell apoptosis in inflammatory demyelinating lesions of chronic myelin oligodendrocyte glycoprotein peptide35-55 induced autoimmune encephalomyelitis was studied in several different gene knockout mice as well as their wild-type counterparts. The gene deletions included tumor necrosis factor (TNF) alpha, lymphotoxin, TNF receptor 1 or 2, Fas-L, inducible nitric oxide synthase, perforin, and interleukin1beta-converting enzyme. Impairment of the TNF receptor 1 pathway led to a 50% reduction of T-cell apoptosis in the central nervous system lesions, whereas the other genetic deletions showed no significant effect. Our study thus identified the TNF receptor 1 signaling pathway as one mechanism responsible for the removal of T lymphocytes from inflammatory demyelinating lesions of the central nervous system. |
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