Both IL-12 receptor and Fc receptor signaling contribute to NK cell cytokine secretion following costimulation with IgG and IL-12. (a) Splenocytes from STAT4^–/– mice or wild-type controls were cultured in the presence of 10 ng/ml rmuIL-12 on plates precoated with 100 μg/ml muIgG. Control wells contained splenocytes cultured with medium alone, muIgG alone, or rmuIL-12 alone. Culture supernatants were harvested after 72 hours and analyzed for muIFN-γ. (b) Human PBMCs were cultured overnight in medium containing 30 μg/ml piceatannol. PBMCs were then cultured with 10 ng/ml rhuIL-12 on plates precoated with huIgG. Standard controls were included. Additional controls included wells containing PBMCs pretreated with medium alone or with medium containing DMSO (the solvent for piceatannol) alone. Culture supernatants were harvested at 72 hours and analyzed for huIFN-γ.