CUTTING EDGE - DIFFERENTIATION OF HUMAN NK CELLS INTO NK1 AND NK2 SUBSETS

Human NK cells cultured in the presence of IL-12 or IL-4 differentiate into cell populations with distinct patterns of cytokine secretion si milar to Th1 and Th2 cells, NK cells grown in IL-12 (NK1) produce IL-1 0 and IFN-gamma, whereas NK cells grown in IL-4 (NK2) produce IL-5 and IL-13, Although these NK cell subsets do not differ in cytotoxic acti vity, NK1 cells express higher levels of cell surface CD95 (Fas) Ag th an NK2 cells and are more sensitive to Ab or chemically induced apopto sis, Like Th1 cells, NK1 cells accumulate much higher levels of the IL -12R beta 2-chain mRNA and are significantly more responsive to IL-12 than NK2 cells at the level of activation of STAT4 transcription facto r. The identification of NK cell subsets that are analogous to T cell subsets suggests a new role for NK cells in innate inflammatory respon ses and in their effect on adaptive immunity.