NK cells regulate CD8+ T cell priming and dendritic cell migration during influenza A infection by IFN-γ and perforin-dependent mechanisms

MQ Ge, AWS Ho, Y Tang, KHS Wong… - The Journal of …, 2012 - journals.aai.org
MQ Ge, AWS Ho, Y Tang, KHS Wong, BYL Chua, S Gasser, DM Kemeny
The Journal of Immunology, 2012journals.aai.org
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 …
Abstract
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-γ, and transfer of IFN-γ–competent naive NK cells into IFN-γ−/− mice restored T cell recruitment, whereas IFN-γ–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-γ−/− and perforin−/− mice showed reduced viral Ag transport by DCs, suggesting that the ability of NK cells to influence virus transport depends on IFN-γ 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.
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