To investigate whether or not plasma IL-15 correlated with NK cell activity, we stimulated elderly cohort D peripheral blood mononuclear cells in vitro with K562 leukemia cells or with low-level IL-12 and immobilized anti-NKp46 antibody, which are well-known NK cell stimuli. Using flow cytometry, we measured the ability of CD56bright and CD56dim NK cells to produce IFN-γ and MIP-1β. We also measured their cytotoxic response, as assayed by the appearance of the CD107a cytotoxic granule marker on the cell surface. Plasma IL-15 level correlated with the CD56dim NK cell MIP-1β and CD107a, but not IFN-γ, responses to NKp46 crosslinking (Table S2 in Supplementary Material). The correlations between NKp46-stimulated responses and plasma IL-15 level remained significant when correcting for age and gender. The responses to NKp46 did not significantly correlate with the responses to K562 leukemia cells, indicating that these two assays measure distinct aspects of NK cell signaling (data not shown). This is not surprising because NK cell responses to K562 largely depend upon NKp30 and NKG2D (25).