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

Wang, Tian; Welte, Thomas

Aged mice, when compared to young adult mice, also displayed a higher content of V4 + cells, another major subpopulation of peripheral  T cells. Depletion of V4 + cells in young mice resulted in a lower mortality following WNV-induced encephalitis [56] . The pathogenic effects of V4 + cells are mediated via the production of proinflammatory and regulatory cytokines during WNV infection ( [56, 71] , see Table 1 ). TNF-ï¡ï€ has been reported to be responsible for BBB compromise and WNV entry into the brain [72] . V4 + cell-depleted mice had reduced TNF- levels in the CNS, accompanied by a decreased viral load in the brain and a lower mortality to WNV encephalitis [56] . V4 + cells also produced IL-17, which is known to increase inflammation by recruiting cells, such as neutrophils or macrophages, to infection sites in several disease models [73, 74] . Nevertheless, the IL-17-producing activity is considered to be dispensable for host immunity against WNV, as in vivo blocking of IL-17 signaling did not affect host susceptibility to WNV infection [71] . V4 + cells also negatively regulate V1 + T cell responses during WNV infection via the production of TGF-ï¢ï€ (Table 1 ). This effect contributes directly to higher viremia, which leads to more virus dissemination into the CNS, and induction of encephalitis [56, 71] . Additionally, the suppressive effects of V4 + cells are associated with decreased IL-10 levels and reduced inflammation in the CNS ( [71] , Table 1 ). IL-10 plays a pathogenic role in host immunity to WNV infection [75, 76] . V1 + cells have been shown to suppress the IL-10-producing CD4 + CD25 + T cells in the lungs of ovalbumin-sensitized and challenged mice [77] . Moreover, V1 + T cells are known to decrease inflammation during bacterial and coxsackievirus infection [52, 78] .