FAS AND FAS LIGAND ENHANCE THE PATHOGENESIS OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS, BUT ARE NOT ESSENTIAL FOR IMMUNE PRIVILEGE IN THE CENTRAL-NERVOUS-SYSTEM

Mutations of CD95 and CD95L, lpr and gld, respectively, are associated with spontaneous autoimmune disease and alteration of immune privileg e, In Ipr or gld animals these processes would he expected to exacerba te experimental allergic encephalomyelitis (EAE), an animal model of t he autoimmune demyelinating disease multiple sclerosis. However, here we show that the Ipr and gld mutations did not overcome the MHC-define d limits of disease and, surprisingly, did not exacerbate the patholog y of EAE on a sensitive haplotype. In fact, the mutations dramatically ameliorated clinical signs of EAE without affecting the development o f a Th1 response or inflammatory cell infiltration into the central ne rvous system, Fewer apoptotic cells were detected in inflammatory lesi ons of lpr mice than in wild-type lesions of similar severity, Our res ults indicate that CD95L is not an instrumental component of immune pr ivilege in the central nervous system, and that functional CD95 and CD 95L are important for the progression of clinical disease.