The inhibitory effect of human interferon alpha on the generation of lymphokine-activated killer activity.

The generation of lymphokine-activated killer (LAK) activity and the proliferative response to human recombinant interleukin-2 (IL-2) were significantly reduced by the presence of human recombinant leukocyte interferon (IFN alpha) in cultures of human peripheral blood mononuclear cells (PBMC). Mature natural killer (NK) cells can be depleted from PBMC with the toxic lysosomotropic agent L-leucine methyl ester. The generation of cytotoxic cells from lymphocytes depleted in leucine methyl ester was also inhibited by indicating that the IFN-alpha effect is not limited to mature cytotoxic NK cells. Depletion of adherent cells from PBMC did not affect the suppression of LAK induction by IFN-alpha. Surface marker analyses of Tac antigen and transferrin receptor (TfR) showed that the presence of IFN alpha throughout the culture period significantly suppressed the typical increase in IL-2-induced Tac- and TfR-positive cells. In contrast, IFN alpha treatment before and after IL-2 culture enhanced LAK cytotoxic activity. Therefore, combinations of these biological response modifiers for clinical use should take into account the dual effect of IFN alpha on key features of the IL-2 response.