Upon introduction of IL-15c to the lung airways, the overall frequency of NK cells isolated from the BAL was significantly increased ( Figure 3A and B) , and the total number of NK cells isolated from this site was nearly three times that of PBS-treated control animals ( Figure 3B ). Interestingly, the percentage of NK cells expressing CD122, the IL-2/15 Rb chain, was reduced in IL-15c-treated animals ( Figure 3B ), perhaps indicative of increased signaling through and subsequent internalization of this receptor complex by IL-15 responsive cells. Unlike T cells, which require large clonal bursts of proliferation to achieve effector status, the effector function of NK cells is more related to activation and mobilization to the site of inflammation [35] . Nevertheless, we wished to test whether the large increases in NK cell number in the lung airways following IL-15c administration could be attributed to IL-15-induced proliferation of NK cells at the site. To assess the potential role of proliferation in this observed increase in NK cell frequency and number in the BAL of treated mice, these NK cells were analyzed for BrdU incorporation. Concomitantly, cells isolated from the BAL were assessed for expression of the cellcycle-specific protein Ki-67. Since BrdU is incorporated into the DNA of only cells in S phase whereas Ki-67 is expressed by cells in any stage of the cell cycle, it was unsurprising that BrdU + cells were only a fraction of Ki-67 + cells ( Figure 3A) . Therefore, we considered only cells positive for both markers as cells undergoing proliferation at the time of treatment. Although the percentage of BrdU-incorporating cells was modestly increased in IL-15c-treated animals, the overall frequency of proliferating cells was low in untreated (,10%) and treated (,12%) animals ( Figure 3B ). These data suggest that IL-15c may trigger the proliferation of NK cells, but proliferation of this cell population in the lung airways is, in general, low and not likely to be solely responsible for the total number of cells extracted from the lung airways. IL-15Ra alone had no significant impact on the accumulation or proliferation of this cell population ( Figure 3A and B) . Finally, differences in cell of CD11c 2 CD11b + cells, CD11c + CD11b 2 cells, and CD3 + NK1.1 + cells from BAL are shown 6 SEM in PBS control (solid lines) or aIL-15-treated (dashed lines) mice (n = 3 mice/group). (E) At the indicated times p.i. with 10 3 pfu HKx31, lung viral titers from PBS and aIL-15-treated mice were determined by plaque assay. Mean viral titer is plotted 6 SEM (n = 2 mice/group on days 1 and 5 p.i. or 3 mice/group for remaining time points; day 2 p = 0.0503). Data are representative of two independent experiments. doi:10.1371/journal.pone.0037539.g002 frequencies, numbers, CD122 expression, and BrdU incorporation were specific to the lung airways (the sight of treatment), as NK cells isolated from spleens were similar in control and IL-15ctreated animals ( Figure 3C and data not shown). Together, these data demonstrate that exogenous IL-15 results in increased numbers of NK cells in the lung airways. Since this increase appeared to be independent of IL-15-mediated effects on cell survival, and proliferation was low, we hypothesized that IL-15 may be responsible for a substantial amount of migration of NK cells into the lung airways following influenza infection similar to its effects on CD8 T cells [19] .