Fas has a crucial role in the progression of experimental autoimmune encephalomyelitis.
To investigate the role of Fas in experimental autoimmune encephalomyelitis (EAE) in mice, we examined the susceptibility of EAE in C57BL/6 (B6).lpr mice lacking Fas. The frequency of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in B6.lpr mice was significantly lower than 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 examination and semiquantitative reverse transcriptase polymerase chain reaction analysis revealed that the infiltration of inflammatory cells and the up-regulation of gene expression for inflammatory cytokines occurred in the central nervous system (CNS) of B6.lpr mice immunized with MOG, even if they showed no clinical sign. These results indicate that Fas may contribute to the pathogenesis of EAE and may play a crucial role in the expansion of inflammation and/or myelin destruction in the CNS rather than in the activation of encephalitogenic T cells in the periphery and/or the breakdown of blood brain barrier.
Okuda
Y
Y
Department of Neurology, Osaka University Medical School, Suita, Japan.
Bernard
C C
CC
Fujimura
H
H
Yanagihara
T
T
Sakoda
S
S
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D017209:Apoptosis; D003433:Crosses, Genetic; D016207:Cytokines / Q000235:genetics; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D013116:Spinal Cord / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D000954:Antigens, Surface; D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger; D019014:fas Receptor