Role of Natural Killer and Gamma-Delta T cells in West Nile Virus Infection

Wang, Tian; Welte, Thomas

δ T cells are important for protective immunity against WNV infection. TCRδ −/− mice, which are deficient in δ T cells, had elevated viremia, as well as more severe encephalitis, and were much more susceptible to WNV infection than were the wild-type controls [54] . The IFN- producing activity partially contributes to their protective effect in host immunity (Table 1) . Upon WNV infection, δ T cells quickly expanded as early as day two and are the major resource for producing IFN-. Furthermore, transfer of splenocytes from TCR −/− IFN −/− mice, which have a defect in the IFN-γ-producing capacity of δ T cells, did not affect host susceptibility in TCRδ −/− mice [54] . Another group also demonstrated that irradiated mice reconstituted with IFN--deficient δ T cells had significantly higher levels of viral loads in the blood and brains during WNV infection than mice reconstituted with IFN--sufficient δ T cells [55] . V1 + cells were the major δ subset producing IFN-. Mice depleted of V1 + cells displayed a phenotype similar to that observed in TCR −/− mice in response to WNV infection ( [56] , Table 1 ). Cytolytic function is another important mechanism of viral control attributed to δ T cells [57] [58] [59] . TCRδ −/− mice had reduced levels of intracellular perforin in splenocytes at day six, post-WNV infection, implying their contribution to cytolytic activity (Table 1 ) [54] . Both CD4 + and CD8 + T cells have been shown to be responsible for the cytolytic activity detected in splenocytes during the first week of WNV infection [60, 61] . We have noted that splenic CD4 + T cells of TCR −/− mice had a lower cytotoxicity potential than those of wild-type mice [62] . Thus, δ T cells may contribute to the cytolytic activity against WNV in the periphery directly and/or indirectly by regulation of αβ T cell response.