IL-15 is critical for the maintenance and innate functions of self-specific CD8(+) T cells.

IL-15 is a pleiotropic cytokine involved in host defense as well as autoimmunity. IL-15-deficient mice show a decrease of memory phenotype (MP) CD8(+) T cells, which develop naturally in naïve mice and whose origin is unclear. It has been shown that self-specific CD8(+) T cells developed in male H-Y antigen-specific TCR transgenic mice share many similarities with naturally occurring MP CD8(+) T cells in normal mice. In this study, we found that H-Y antigen-specific CD8(+) T cells in male but not female mice decreased when they were crossed with IL-15-deficient mice, mainly due to impaired peripheral maintenance. The self-specific TCR transgenic CD8(+) T cells developed in IL-15-deficient mice showed altered surface phenotypes and reduced effector functions ex vivo. Bystander activation of the self-specific CD8(+) T cells was induced in vivo during infection with Listeria monocytogenes, in which proliferation but not IFN-gamma production was IL-15-dependent. These results indicated important roles for IL-15 in the maintenance and functions of self-specific CD8(+) T cells, which may be included in the naturally occurring MP CD8(+) T-cell population in naïve normal mice and participate in innate host defense responses.