Highly pathogenic influenza A viruses cause acute severe pneumonia to which the occurrence of "cytokine storm" has been proposed to contribute. Here we show that interleukin-15 (IL-15) knockout (KO) mice exhibited reduced mortality after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) albeit the viral titers of these mice showed no difference from those of control mice. There were significantly fewer antigen-specific CD44(+) CD8(+) T cells in the lungs of infected IL-15 KO mice, and adoptive transfer of the CD8(+) T cells caused reduced survival of IL-15 KO mice following influenza virus infection. Mice deficient in beta(2)-microglobulin by gene targeting and those depleted of CD8(+) T cells by in vivo administration of anti-CD8 monoclonal antibody displayed a reduced mortality rate after infection. These results indicate that IL-15-dependent CD8(+) T cells are at least partly responsible for the pathogenesis of acute pneumonia caused by influenza A virus.