γδ T cells promote the maturation of dendritic cells during West Nile virus infection

gamma delta T cells are important for the early control of West Nile virus (WNV) dissemination. Here, we investigated the role of gamma delta T cells in the regulation of CD4+ T-cell response following a WNV challenge. Splenic dendritic cells (DCs) of WNV-infected gamma delta T-cell-deficient (TCR delta-/-) mice displayed lower levels of CD40, CD80, CD86 and major histocompatibility complex (MHC) class II expression and interleukin-12 (IL-12) production than those of wild-type mice. Naive DCs cocultured with WNV-infected gamma delta T cells showed enhanced levels of costimulatory molecules, MHC class II expression and IL-12 production. Further, coculture of CD4+ T cells from OT II transgenic mice with DCs of WNV-infected TCR delta-/- mice induced less interferon-gamma (IFN-gamma) and IL-2 production than with those of wild-type controls. Viral antigens were detected in WNV-infected gamma delta T cells.WNV infection or toll-like receptor (TLR) agonist treatment of gamma delta T cells induced the production of IFN-gamma, tumor necrosis factor-alpha and IL-6, which are known to promote DC maturation. Nevertheless, the levels of TLRs 2, 3, 4 and 7 expression of WNV-infected gamma delta T cells were not different from those of noninfected cells. Overall, these data suggest that WNV-induced gamma delta T-cell activation promotes DC maturation and initiates CD4+ T-cell priming.