NK Cells Regulate CD8+ T Cell Priming and Dendritic Cell Migration during Influenza A Infection by IFN-γ and Perforin-Dependent Mechanisms

An effective immune response against influenza A infection depends on the generation of virus-specific T cells. NK cells are one of the first-line defenses against influenza A infection. We set out to delineate the role of NK cells in T cell immunity using a murine model of influenza A infection with A/PR/8/34. We show that early T cell recruitment mainly occurs in the posterior mediastinal lymph node (pMLN). Depletion of NK cells significantly impaired both dendritic cell (DC) and T cell recruitment into the pMLN.A similar reduction of T cell recruitment was observed when migration was blocked by pertussis toxin, suggesting that migration of pulmonary NK cells and DCs regulates cell recruitment to the pMLN.T cell recruitment was dependent on IFN-gamma, and transfer of IFN-gamma-competent naive NK cells into IFN-gamma(-/-) mice restored T cell recruitment, whereas IFN-gamma-deficient NK cells failed to do so. In addition, NK cell depletion reduced the uptake and transport of influenza A virus by DCs, and significantly impaired the virus-specific T cell response. Both IFN-gamma(-/-) and perforin(-/-) mice showed reduced viral Ag transport by DCs, suggesting that the ability of NK cells to influence virus transport depends on IFN-gamma and perforin. In summary, our data suggest that NK cells play a critical role in the initiation and shaping of the T cell response after influenza A infection. The Journal of Immunology, 2012, 189: 2099-2109.