Since co-expression of CD122 and CD132 render NK cells responsive to IL-15 signals, we next wished to determine whether virally induced IL-15 and subsequent signaling through these receptors affected the accumulation of these cells in the respiratory tract. Because IL-15 2/2 mice exhibit a severe developmental defect in both NK and NKT cell lineages and are nearly devoid of these cell populations [20] , we chose to use an anti-IL-15 blocking antibody to selectively deplete IL-15 concurrent with infection. Therefore, we monitored the influx of NK cells in animals receiving either PBS or anti-IL-15 mAb administered i.p. daily from day 0 through day 4 post influenza infection. In order to more accurately define bona fide NK cells, particularly in the lung airways harboring few NK cells at very early time points post influenza infection, we included NKp46 reactivity in our staining protocol and henceforth define NK cells as CD3 2 lymphocytes positive for both NK1.1 and NKp46. While NK cells accumulated in the lung airways of untreated mice as expected, by day 2 p.i. the overall frequency of NK cells in IL-15 blocked animals was reduced by half and remained this low through day 4 p.i. (Figure 2A) . Concordantly, total numbers of NK cells in IL-15blocked mice were partially reduced at day 2 p.i., and substantially (Figure 2A ). In fact, whereas the numbers of NK cells continued to accumulate in the lung airways of control-treated animals through day 4 p.i., numbers of NK cells in the lung airways of treated animals plateaued by day 3 p.i. (Figure 2A ). In the lung parenchyma of control-treated animals, NK cells also accumulated over time post infection, similar to those in the lung airways, but the frequencies of NK cells in this site remained unchanged in IL-15-blocked mice. Numbers of NK cells in the lung parenchyma of anti-IL-15 treated animals also remained similar to control animals with only a slight reduction at day 2 p.i. ( Figure 2B ). Importantly, while the numbers of NK cells were significantly reduced at the site of infection as a result of an IL-15 deficiency, anti-IL-15 treatment had little effect on the frequency or number of NK cells found in anatomical sites distal to the site of infection such as the spleen ( Figure 2C ). In order to determine whether an absence of IL-15 in the lung airways resulted in the reduced frequencies and numbers of NK cells specifically, numbers of other populations of innate cells in the airways at these early time points post infection were analyzed. CD11c 2 CD11b + cells (granulocytes) or CD11c + CD11b 2 (dendritic cells) in the airways following infection were mostly unaffected by the IL-15 deficiency, with only a small reduction observed at day 4 p.i. (Figure 2D ). In contrast, NK1.1 + CD3 + (NKT cells) were markedly reduced in the lung airways of IL-15blocked mice ( Figure 2D ), but overall, these cells represented a low proportion of the innate cells responding to influenza infection at these early time points following infection ( Figure 1A ). Together, these data indicated that short term blockade of IL-15 did not result in global defects in NK cell homeostasis or survival in peripheral tissues and the effects of IL-15 were largely specific to NK cells as blocking IL-15 selectively resulted in a significant loss of NK cells recovered from the site of infection.