FAS HAS A CRUCIAL ROLE IN THE PROGRESSION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

To investigate the role of Fas in experimental autoimmune encephalomye litis (EAE) in mice, we examined the susceptibility of EAE in C57BL/6 (B6).lpr mice lacking Fas. The frequency of myelin oligodendrocyte gly coprotein (MOG)-induced EAE in B6.lpr mice was significantly lower tha n that in B6 mice (19% vs 94%). However? no significant difference was observed between them in either the lymphocyte proliferation response or antibody reactivity to MOG. In addition? the histological examinat ion and semiquantitative reverse transcriptase-polymerase chain reacti on analysis revealed that the infiltration of inflammatory cells and t he up-regulation of gene expression for inflammatory cytokines occurre d in the central nervous system (CNS) of B6.lpr mice immunized with MO G, even if they showed no clinical sign. These results indicate that F as may contribute to the pathogenesis of EAE and may play a crucial ro le in the expansion of inflammation and/or myelin destruction in the C NS rather than in the activation of encephalitogenic T cells in the pe riphery and/or the breakdown of blood brain barrier. (C) 1998 Elsevier Science Ltd. All rights reserved.