LYMPHOKINE-ACTIVATED KILLER (LAK) CELLS - INTERFERON-GAMMA SYNERGIZES WITH INTERLEUKIN-2 TO INDUCE LAK CYTOTOXICITY IN HOMOGENEOUS LEUKEMIC PREPARATIONS

Lymphokine-activated killer (LAK) cells are generated by the incubation of lymphocytes with high levels of interleukin-2 (IL-2). We report here that interferon-γ (IFN-γ) acts synergistically with low levels of IL-2 to promote LAK differentiation in peripheral blood lymphocytes as well as in homogeneous T acute lymphocytic leukemic cells exhibiting LAK precursor reactivity. No augmentation of LAK response was observed with IFN-α-2, IFN-β-1, and IFN-β-2 IL-6. The synergism between IL-2 and IFN-γ was expressed in the ability of activated lymphocytes to lyse natural killer resistant cell line targets and surgically removed melanoma cells. The augmented LAK response due to IFN-γ does not reflect up-regulation of the high-affinity IL-2 receptors consisting both of α and β subunits, since expression of the α (Tac) subunit on the responding leukemic cells was not increased by IFN-γ. The observed IFN-γ IL-2 synergism in the induction of monoclonal LAK precursors suggests that a single precursor cell responds to both IFN-γ and IL-2 and that different mechanisms underlie the basal IL-2-mediated LAK response and its enhancement by IFN-γ. © 1991.