Effects of Recombinant Interferon-Gamma and Interleukin-2 on the Generation of Lymphokine-Activated Killer Cells in Vitro

In order to determine if recombinant interferon-gamma (rIFN-gamma) can augment the effect of recombinant interleukin-2 (rIL-2) in generating lymphokine-activated killer (LAK) cells, we have incubated normal peripheral blood mononuclear cells (PBMC) with these lymphokines for 3 days and then tested their LAK and natural killer (NK) cell activity. We have found that LAK activity in PBMC from 13 out of 13 normal donors was increased by the combined lymphokines above that due to either lymphokine alone, provided that rIL-2 was present at suboptimal concentration: Optimal levels of rIFN-gamma (100 U/ml) were able to enhance the LAK-inducing activity of suboptimal levels (5 U/ml) but not optimal levels (100 U/ml) of rIL-2. NK activity showed a similar response to these concentrations of lymphokines. Activation of LAK/NK cells was accompanied by increases in the percentages of Leu 19+ (CD56) cells and TAC+ (IL-2-receptor) cells, and in the intensity of TAC antigen expression. These results indicate that combination rIFN-gamma and rIL-2 may be more effective in generating LAK/NK cells than rIL-2 alone, particularly with suboptimal concentrations of rIL-2 such as occur during continuous infusion therapy with this agent.