The Vγ4(+) cells, a subpopulation of peripheral γδ T cells, are involved in West Nile virus (WNV) pathogenesis, but the underlying mechanism remains unclear. In this study, we found that WNV-infected Vγ4(+) cell-depleted mice had lower viremia and a reduced inflammatory response in the brain. The Vγ4(+) cells produced IL-17 during WNV infection, but blocking IL-17 signaling did not affect host susceptibility to WNV encephalitis. We also noted that there was an enhanced magnitude of protective splenic Vγ1(+) cell expansion in Vγ4(+) cell-depleted mice compared to that in controls during WNV infection. In addition, Vγ4(+) cells of WNV-infected mice had a higher potential for producing TGF-β. The γδ T cells of WNV-infected Vγ4(+) cell-depleted mice had a higher proliferation rate than those of WNV-infected controls upon ex vivo stimulation with anti-CD3, and this difference was diminished in the presence of TGF-β inhibitor. Finally, Vγ4(+) cells of infected mice contributed directly and indirectly to the higher level of IL-10, which is known to play a negative role in immunity against WNV infection. In summary, Vγ4(+) cells suppress Vγ1(+) cell expansion via TGF-β and increase IL-10 level during WNV infection, which together may lead to higher viremia and enhanced brain inflammation.
© 2011 Federation of European Microbiological Societies.