Okuda Y, Bernard C C, Fujimura H, Yanagihara T, Sakoda S
Department of Neurology, Osaka University Medical School, Suita, Japan.
Mol Immunol. 1998 Apr;35(5):317-26. doi: 10.1016/s0161-5890(98)00049-2.
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.
为研究Fas在小鼠实验性自身免疫性脑脊髓炎（EAE）中的作用，我们检测了缺乏Fas的C57BL/6（B6）.lpr小鼠对EAE的易感性。B6.lpr小鼠中髓鞘少突胶质细胞糖蛋白（MOG）诱导的EAE发生率显著低于B6小鼠（19%对94%）。然而，它们在淋巴细胞增殖反应或对MOG的抗体反应性方面均未观察到显著差异。此外，组织学检查和半定量逆转录聚合酶链反应分析显示，用MOG免疫的B6.lpr小鼠中枢神经系统（CNS）中发生了炎性细胞浸润和炎性细胞因子基因表达上调，即便它们没有表现出临床症状。这些结果表明，Fas可能参与EAE的发病机制，并且可能在中枢神经系统炎症扩展和/或髓鞘破坏中起关键作用，而非在外周致脑炎T细胞激活和/或血脑屏障破坏中起关键作用。
