Functionally distinct subsets of natural killer cells help shape and regulate the immune response during viral infection (INC8P.429)

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Abstract Natural killer (NK) cells are innate lymphocytes that play an important role in the immune response against certain viral infections and transformed cells. Historically, NK cells have been recognized for their direct antiviral defense; however, a more complex view of NK cell function has recently emerged highlighting their ability to direct the balance between viral infection and host immunity. While the diverse effector functions of NK cells are increasingly seen as vital components of host immunity, the specific populations of NK cells that mediate these differential effects have not been identified. In this study, we provide evidence for distinct NK cell subsets that differ in their effector and immunoregulatory functions during influenza infection. We show here that during the early stages of the host immune response to viral infection, a population of effector NK cells directly contributes to viral resistance at the site of infection, while a separate helper NK subset concurrently functions to prime the adaptive immune response by expanding dendritic cells in the lymph nodes. Conversely, at the later stages of viral infection, a subset of suppressor NK cells dampens the adaptive immune response by directly regulating antigen-specific T cells. These results suggest that adoptive transfer of specific NK subsets may serve as a useful therapeutic strategy to modulate the immune response during viral infection.