Both CD56^bright and CD56^dim NK cells are activated and express IFN-γ in response to IL-12 and IL-18. (A) Freshly isolated human PBLs were left untreated, stimulated with IL-12 and IL-18 (20 ng/mL each), or with PMA and ionomycin for 4 hours in the presence of Brefeldin A. Expression of intracellular IFN-γ and cell surface markers CD3, CD56, and CD69 was assessed by 2-color flow cytometry. Percentages of cells in top left, top right, and bottom right quadrants are indicated. (B) NK cells were purified by negative selection and left untreated or stimulated with IL-12 and IL-18 (20 ng/mL each) for 4 hours. Cell surface CD56 and intracellular IFN-γ expression were assessed by flow cytometry. Percentages of cells present in each quadrant are indicated.