Enhanced IFN-γ production by human memory-like NK cells is associated with a CD94⁺NKG2A⁺CD57⁻KIR⁻CD69⁺ phenotype. Purified NK cells (≥ 95% CD56⁺CD3⁻) were cultured as in Figure 1A for 7 days and assessed for IFN-γ in concert with the indicated cell surface marker after 6 hours of IL-12 + IL-15 restimulation. (A) Representative bivariate flow plots from control and IL-12 + IL-18–preactivated NK cells showing correlation of IFN-γ production (all were restimulated with IL-12 + IL-15) in populations positive or negative for CD94, NKG2A, NKG2C, KIR, CD57, and CD69. (B) Because CD56^bright NK cells had > 95% or < 10% expression of CD94, NKG2A, KIR, and CD57 (Figure 6), IFN-γ correlative data are shown gated on CD56^dim NK cells. There were a greater percentage of IFN-γ⁺ NK cells in the CD94⁺, NKG2A⁺, NKG2C⁺, and CD69⁺ fractions of CD56^dim NK cells. In contrast, there were a significantly greater percentage of IFN-γ⁺ NK cells in CD57⁻ and KIR⁻ CD56^dim NK cells. There were no significant correlations of NKG2C or CD69 expression with IFN-γ production in CD56^bright NK cells (not shown). Statistical comparisons are between marker positive and negative preactivated or control NK cell association with IFN-γ. A larger number of donors were assessed for CD94, NKG2A, and CD57 correlations to assess the more subtle differences between marker positive and negative control cells (n = 4-17 donors; 2-6 independent experiments). *P < .05; **P < .01; ***P < .001.