NK dendritic cells expanded in IL-15 exhibit antitumor responses in vivo.

NK dendritic cells (NKDC) are a novel subtype of DC with NK cell properties. IL-15 is a pleiotropic cytokine that plays an obligate role in the proliferation and survival of NK cells. We hypothesized that IL-15 is also essential for NKDC development. NKDC were nearly absent in IL-15(-/-) mice, but restored by administration of exogenous IL-15. Treatment of wild-type mice with IL-15 caused a 2- to 3-fold expansion of both NK cells and NKDC. After 7 days of culture with IL-15, sorted splenic NKDC expanded 10-fold while NK cells increased 5-fold. NKDC expanded in IL-15 retained their cytolytic capacity but lost the ability to stimulate naive T cells. Meanwhile, NKDC expanded in IL-15 produced 10 times more IFN-gamma as fresh NKDC and conferred protection in a tumor prevention model. Thus, IL-15 is essential to the proliferation and survival of NKDC and IL-15 expanded NKDC possess antitumor properties.