Role of two distinct γδ T cell subsets during West Nile virus infection

gamma delta T cells respond rapidly following West Nile virus (WNV) infection, limiting viremia and invasion of the central nervous system and thereby protecting the host from lethal encephalitis. Here, we investigated the role of two major subpopulations of peripheral gamma delta T cells, V gamma 1(+) and V gamma 4(+) cells, in host immunity against WNV infection. We found initially that aged mice were more susceptible to WNV infection than young mice. Following WNV challenge, V gamma 1(+) cells in young mice expanded significantly whereas V gamma 4(+) cells expanded modestly. In contrast, aged mice exhibited a slower and reduced response of V gamma 1(+) cells but maintained a higher content of V gamma 4(+) cells. V gamma 1(+) cells were the major gamma delta subset producing IFN-gamma during WNV infection. Mice depleted of V gamma 1(+) cells had an enhanced viremia and higher mortality to WNV encephalitis. V gamma 4(+) cells had a higher potential for producing tumor necrosis factor-alpha (TNF-alpha), a cytokine known to be involved in blood-brain barrier compromise and WNV entry into the brain. Depletion of V gamma 4(+) cells reduced TNF-alpha level in the periphery, accompanied by a decreased viral load in the brain and a lower mortality to WN encephalitis. These results suggest that V gamma 1(+) and V gamma 4(+) cells play distinct roles in protection and pathogenesis during WNV infection.