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

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-15Ralpha-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(-/-) x 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 gamma signaling cytokines during their response against viral infection.