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

T-cell apoptosis in inflammatory demyelinating lesions of chronic myelin ol igodendrocyte glycoprotein peptide(35-55) induced autoimmune encephalomyeli tis was studied in several different gene knockout mice as well as their wi ld-type counterparts. The gene deletions included tumor necrosis factor (TN F) alpha, lymphotoxin, TNF receptor 1 or 2, Fas-L, inducible nitric oxide s ynthase, perforin, and interleukin1 beta-converting enzyme. Impairment of t he 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 signal ing pathway as one mechanism responsible for the removal of T lymphocytes f rom inflammatory demyelinating lesions of the central nervous system.