Different combinations of cytokines and activating receptor stimuli are required for human natural killer cell functional diversity

► We compared the effects of several cytokine combinations on NK cell function. ► IL21 + IL2 induced a synergistic effect on degranulation but not on cytokine production. ► Optimal cytokine production was induced by IL21 + IL15. ► Higher production of TNFα was shown in the CD56dim subset after NKp46 engagement. ► Different cytokines combined with selected NK receptor stimuli can help to dissect NK responses.