Here, we have demonstrated that NK cells, which accumulate in the lung airways early after influenza infection, are dependent on IL-15 for this accumulation and subsequent ability to control viral load. NK cells in the lung airways express high levels of the common gamma chain (CD132) and CD122, receptors responsible for imparting IL-15 responsiveness. Since IL-15 is known to be produced in the lung airways following influenza infection, we investigated the role of IL-15 in NK cell responses to influenza. In the absence of IL-15, NK cell frequencies and numbers were significantly reduced in the BAL, resulting in impaired early control of influenza virus. Although numbers of CD3 + NK1.1 + cells were also substantially reduced following anti IL-15 treatment, it is unclear whether this cell population plays a relevant role in controlling primary infections with influenza. While NK cells are thought to be very important participants in the control of influenza replication, evidence for NKT cells playing a similar role is more controversial [38] . Models of NKT cell activation using aGal-Cer revealed enhanced innate responses to influenza and improved disease outcome [39] , but challenge of CD1d 2/2 mice with influenza led to increased survival, implying an immuno-regulatory role for NKT cells in this model [40] . Whether or not these cells are critically involved in viral clearance, in our model, they represent a very small percentage (,1%) of the lymphocytes in the lung airways in the first five days following infection. Therefore, we believe that an abrogation of virallyinduced IL-15 in the lung airways most dramatically affects CD3 2 , NK1.1, NKp46 double positive NK cells responding rapidly to infection. By the same principle, exogenous IL-15 could be used therapeutically to increase NK cell populations in the BAL-primarily as a result of IL-15-induced migration-to enhance viral control. Therefore, these combined data indicate that influenza-induced IL-15 is an important signal for the migration of NK cells to the lung airways where they help limit viral replication.