Study of the mechanism for in vitro activation of mouse NK cells by interferon.

The enhancement of the lytic capacity of mouse splenic 'natural killer' (NK) cells by interferon has been studied in vitro as a model for NK cell differentiation from inactive immediate precursors. We show that the increased cytotoxicity is a function of interferon concentration, and that two stages in the NK cell differentiation pathway can be distinguished. The first, very brief, can be performed at 0 degree C and without protein synthesis and probably corresponds to the fixation of interferon on its cell surface receptors. The second, resulting from the inductive signal given by interferon, proceeds for several hours and requires both RNA and protein synthesis. Our results also indicate that target cells for interferon-induced cytotoxicity are cells with 'null' characteristics, similar to the mature NK cells. Finally, they suggest that no soluble intermediary factor other than interferon is involved in the enhancing of NK cell cytotoxicity.