West Nile virus (WNV) is a neurotropic flavivirus that causes
encephalitis, most frequently in elderly and immunocompromised humans. Previous studies demonstrated that CD8+ T cells utilize
perforin-dependent cytolytic mechanisms to limit
WNV infection. Nonetheless, the phenotype of
perforin-deficient CD8+ T cells was not as severe as that of an absence of CD8+ T cells, suggesting additional effector control mechanisms. In this study, we evaluated the contribution of Fas-
Fas ligand (FasL) interactions to CD8+ T-cell-mediated control of
WNV infection. Notably, the cell death
receptor Fas was strongly upregulated on neurons in culture and in vivo after
WNV infection. gld mice that were functionally deficient in FasL expression showed increased susceptibility to lethal
WNV infection. Although
antigen-specific priming of CD8+ T cells in peripheral lymphoid tissues was normal in gld mice, increased central nervous system (CNS) viral burdens and delayed clearance were observed. Moreover, the adoptive transfer of WNV-primed wild-type but not gld CD8+ T cells to recipient CD8(-/-) or gld mice efficiently limited
infection in the CNS and enhanced survival rates. Overall, our data suggest that CD8+ T cells also utilize FasL effector mechanisms to contain
WNV infection in Fas-expressing neurons in the CNS.