CHARACTERIZATION AND MODULATION OF HUMAN LYMPHOKINE (INTERLEUKIN-2) ACTIVATED KILLER-CELL INDUCTION

Abstract

Culture of human peripheral blood mononulear cells with purified interleukin 2 (IL-2) results in the induction of a cytotoxic population of cells capable of lysing autologous tumor cells and natural killer (NK) cell resistant tumor cell lines. The current study was undertaken to characterize biological agents which might modulate the induction of lymphokine (IL-2) activated killer (LAK) cells and to optimize culture conditions for LAK cell induction. Preliminary studies were undertaken to characterize optimal time and IL-2 concentration for induction of LAK cell activity. Subsequently, we demonstrated that: (a) LAK cell induction is inhibited at high (2.5 .times. 106/ml) cell concentrations and this phenomenon is due to the presence of monocytes; (b) depletion of monocytes allows LAK cell induction at 5-10-fold higher cell concentrations without altering the extent or range of LAK-cell activity; (c) interleukin 1 enhances and .alpha.- and .beta.-interferons inhibit IL-2 induced proliferation, without altering LAK cell induction; and (d) .gamma.-interferon alters neither IL-2 induction of proliferation nor LAK cell activity.