Intranasal administration of IL-15c during the innate phase of the immune response against influenza improves early control of viral control.

<p>On days 1–4 post infection with 10³ pfu HKx31 i.n., animals received either PBS vehicle control (Black circles) or IL-15c (red squares) i.n. (A). Whole lungs were collected and analyzed via plaque assay for viral titer on days 2, 4, 6, and 8 p.i. (B). Significant differences between control and IL-15c-treated mice were observed on days 4 (C) and 6 (D) p.i. (*p = 0.022 and 0.013).</p

Administration of IL-15c i.n. increases the number of NK cells recovered from the lung airways.

<p>On day 3 p.i. with 10³ pfu HKx31, mice were administered either PBS vehicle control (black bars), IL-15Rα alone (shaded bars) or IL-15c (open bars) intranasally. Twelve hours post treatment, CD3⁻ lymphocytes were analyzed for NK1.1 and NKp46 expression. These NK cells were quantified and analyzed for CD122 expression, BrdU incorporation, and Ki-67 staining. Representative flow plots are depicted in panel (A), and graphical representations of mean frequencies and numbers of NK cells ± SEM, as well as percentage of these cells positive for CD122 and BrdU are depicted in panel (B) (n = 3 mice/group; * = p<0.025). (C) Mean frequencies and numbers of NK cells in the spleen are plotted ± SEM (n = 3 mice/group). Data are representative of two independent experiments.</p

NK1.1+ NK cells are partially required for the subsequent accumulation of influenza-specific CD8 T cell accumulation at the site of infection.

<p>Beginning on the day of infection, mice received i.v. injections of either PBS vehicle control or αNK1.1 (PK136) every other day until day 6 p.i. (red arrows), and indicated tissues were collected on days 4, 6, and 8 p.i. (A). Mean number NK cells cells on day 4 p.i. in untreated (black bars) and PK136-treated (open bars) are shown ± SEM (n = 3 mice/group) (B). Mean number of NP-Tet⁺ CD8 T cells in the BAL, lung, and spleen were quantified and depicted ± SEM on day 6 (C) and day 8 (D) p.i. (n = 3 mice/group). Stars indicate statistical significance (*p = 0.009). Data are representative of three independent experiments.</p

IL-15 is chemotactic for NK cells in vitro.

<p>Three days following infection with 10³ pfu HKx31 i.n., 1×10⁶ bulk lymphocytes from the pooled BAL, lung, and spleen of 8 mice were placed in the top chamber of a transwell with the bottom chamber containing 500 µL either media alone (black bars) or supplemented with 100 ng IL-15c (open bars). Mean percent migration of CD3⁻, NK1.1⁺ NK cells is depicted ± SEM (n = 3 replicates/group; *p = 0.046 and 0.003). Data are representative of three independent experiments. Significant differences in migration to media alone or media containing IL-15c are indicated by stars (*p<0.05).</p