Cutting Edge: Murine NK Cells Degranulate and Retain Cytotoxic Function without Store-Operated Calcium Entry

Sustained Ca 2+ signaling, known as store-operated calcium entry (SOCE), occurs downstream of immunoreceptor engagement and is critical for cytotoxic lymphocyte signaling and effector function. CD8 + T cells require sustained Ca 2+ signaling for inflammatory cytokine production and the killing of target cells; however, much less is known about its role in NK cells. In this study, we use mice deficient in stromal interacting molecules 1 and 2, which are required for SOCE, to examine the contribution of sustained Ca 2+ signaling to murine NK cell function. Surprisingly, we found that, although SOCE is required for NK cell IFN-γ production in an NFAT-dependent manner, NK cell degranulation/cytotoxicity and tumor rejection in vivo remained intact in the absence of sustained Ca 2+ signaling. Our data suggest that mouse NK cells use different signaling mechanisms for cytotoxicity compared with other cytotoxic lymphocytes.