Cutting Edge: IL-15-Independent NK Cell Response to Mouse Cytomegalovirus Infection

Abstract

NK cells respond rapidly during viral infection. The development, function, and survival of NK cells are thought to be dependent on IL-15. In mice lacking IL-15, NK cells are found in severely decreased numbers. Surprisingly, following infection of IL-15- and IL-15Rα-deficient mice with mouse CMV, we measured a robust proliferation of Ly49H-bearing NK cells in lymphoid and nonlymphoid organs capable of cytokine secretion and cytolytic function. Remarkably, even in Rag2−/− × Il2rg−/− mice, a widely used model of NK cell deficiency, we detected a significant number of NK cells 1 wk after mouse CMV infection. In these mice we measured a >300-fold expansion of NK cells, which was dependent on recognition of the m157 viral glycoprotein ligand and IL-12. Together, these findings demonstrate a previously unrecognized independence of NK cells on IL-15 or other common γ signaling cytokines during their response against viral infection.