Augmentation of interleukin 2-activated cytotoxicity after treatment of cells with inhibitors of interferon production.

Low-density human lymphocytes cultured with recombinant interleukin 2 (rIL-2) generated a high level of interferon(s) (IFN). Consistently more IFN including IFN-tau was produced during the first 3 days of culture with rIL-2 than during the subsequent 4 days. That ability was mainly associated with mepacrine+ cells and was decreased by low concentrations of leucine methyl ester (Leu-O-Me) or ammonium chloride. Leu-O-Me was employed either for the pretreatment of cells before the culture or as the additive to culture medium. The decrease in IFN production after pretreatment was associated with enhanced rIL-2-activated cytotoxicity. Similarly, 1 mM of ammonium chloride or 1 mM of Leu-O-Me added to rIL-2 supplemented cultures for 3 days showed an association between inhibition of IFN-tau generation and increased activation of cytotoxic activity. Thus NK cells appear to regulate their own response to rIL-2 activation and the control mechanism seems to be associated with the ability of the cells to produce IFN(s) and possibly other cytokines.