Activation of Human Natural Killer Cells Cytotoxic for Human Leukemia Cells by Purified Interferon

Abstract

Interferon (IF) inducers and IF-containing preparations of leukocyte origin have recently been reported to augment natural killer (NK) cell activity. Our studies were undertaken to determine whether highly purified human fibroblast interferon (HFIF), induced by polyinosinic: polycytidylic acid (poly I:C), would augment human NK cell activity against an NK-sensitive leukemia cell line, K562, and, more importantly, to determine whether HFIF would activate normal lymphocytes to lyse human leukemia cells that have not been adapted to tissue culture or established as cell lines. Pretreatment of peripheral blood mononuclear cells for 1 to 16 hr with purified HFIF (150 to 300 units/ml) caused 2.5- to 5-fold increases in cytotoxicity against the K562 cells. Both native and HFIF-augmented cytotoxicities were mediated by FcR⁺ lymphocytes (lymphocytes expressing receptors for the Fc portion of IgG). Removal of FcR⁺ lymphocytes, but not monocytes, prevented HFIF from augmenting cytotoxicity, suggesting that HFIF activates preexisting FcR⁺ NK cells and that monocytes are not required for this effect. Our findings that NK cell activity is augmented by poly I:C-induced fibroblast IF, which lacks lymphokines and viral products present in virus-induced leukocyte IF preparations previously used, together with the fact that our IF preparation was more highly purified than any previously used for such studies, strongly suggest that the IF protein itself augments NK activity. HFIF-treated cells from some individuals lysed many patients' leukemia cells; however, the HFIF-treated cells were not cytotoxic for autologous or allogeneic normal lymphocytes or concanavalin A blasts. FcR⁺ cells were required for the HFIF-induced cytotoxicity against the patients' leukemia cells. These results thus demonstrate that not only leukemia cell lines, but also human leukemia cells that have not been adapted to tissue culture or established as cell lines, can be lysed by IF-activated human NK cells.