FAS-DEFICIENT AND FASL-DEFICIENT MICE ARE RESISTANT TO INDUCTION OF AUTOIMMUNE ENCEPHALOMYELITIS

Experimental autoimmune encephalomyelitis (EAE) is an organ-specific a utoimmune disease inducible in susceptible animals bf myelin Ag-specif ic CD4(+) Th1 cells. The mechanisms by which these cells induce inflam mation and demyelination in the central nervous system (CNS) are incom pletely understood. To determine the roles of Fas and FasL in the invo lvement of CNS autoimmune injury, we determined susceptibility to EAE of Fas- or FasL-deficient mice. Compared with wild-type mice, mice exp ressing lpr (Fas) and gld (FasL) mutations were relatively resistant t o the development of clinical EAE, and this correlated with fewer infl ammatory infiltrates and cells undergoing apoptosis in the CNS of the mutant mice. The gld and lpr mice, however, developed significant T ce ll responses with production of Th1 cytokines in response to the encep halitogenic myelin peptide. These results suggest that the Fas/FasL pa thway plays a critical role in the development of EAE probably by medi ating apoptosis within the target tissue.