More CD57⁺CD56^dimCD16⁺ NK cells produce IFN-γ in response to activation by CD16, but they are less responsive to IL-12 and IL-18. Enriched NK cells were activated for 6 hours with different cytokines (A), with anti-CD16 at 10 μg/mL (B), with anti-CD16 at different concentrations (0.5, 1, or 10 μg/mL) and 200 IU/mL IL-2 (C), with plate-bound antibodies at 10 μg/mL and 200 IU/mL IL-2 (D), or with K562 or 721.221 target cells and 200 IU/mL IL-2 (E). CD56^dimCD16⁺ NK cells were gated on CD57⁺ and CD57⁻ cells, and the percentages of cells expressing IFN-γ were determined in each subset (A-E). The gMFI of IFN-γ staining of each subset is shown (A-C). Only minimal amounts of IFN-γ were detected in NK cells cultured in either IL-12 or IL-18 alone (not shown), similar to the amount detected in NK cells cultured in IL-2 alone (A). Black bars represent CD57⁺; and white bars, CD57⁻. **P < .005. ***P < .0005. P values were determined between CD57⁺ and CD57⁻ NK cells (n = 8).