Differential Effects of Recombinant Interferons α, β, and γ on Induction of Human Lymphokine (IL–2)–Activated Killer Activity

Abstract

The effects of three classes of recombinant interferons (IFN–αA, IFN–β, and IFN-γ)on maximal induction of lymphokine (IL–2)-activated killer (LAK) activity were studied. Highly purified lymphocytes (>99%) were obtained by counter-flow centrifugal elutriation from peripheral blood of healthy donors. After incubation for 4 days with IL-2 (1 U/ml), purified lymphocytes showed maximal LAK activity against NK cell-resistant target (Daudi) cells, as assessed by 4-hour ⁵¹Cr release assay. Addition of exogenous IFN-αA or IFN-β to cultures of lymphocytes plus IL-² resulted in significant inhibition of LAK activity, but addition of IFN-γ had no effect on LAK induction by IL-². IFN–αA caused greatest inhibition of LAK activity when added at the start of culture of lymphocytes with IL-², and was less inhibitory when added 1 day later. Similar inhibition by IFN-αA or IFN-β was observed with nine lines of human tumorigenic cells as targets of LAK activity. IFN-αA and IFN-β also inhibited the proliferative responses of lymphocytes to IL–² stimulation, and the expression of IL-²receptors on their surface, whereas IFN-γ did not. These results suggest that IFN-αA and IFN-β may be important in in situ regulation of LAK cell induction against neoplasms. [J Natl Cancer Inst 1988;80:425-431]