Natural killer cell-mediated inhibition of growth of myeloid and lymphoid clonogenic leukemias.

We have shown that peripheral blood (PB) lymphocytes of normal donors inhibit colony formation by myeloid (K-562) and lymphoid (Molt-4) leukemia cell lines in a clonogenic assay in vitro. The inhibitor cells were identified as natural killer (NK) cells based on their large granular lymphocyte (LGL) morphology and CD16+CD5- cell surface phenotype. The levels of inhibition were dependent both on the leukemia: effector (L:E) cell ratio, as well as on the time of preincubation of the leukemic and effector cells; maximum inhibition was observed at a 1:20 L:E cell ratio, and required 6-16 h preincubation of the leukemia and effector cells. Colony formation of both K-562 and Molt-4 was also inhibited by a soluble factor derived from coculture of K-562 and PB lymphocytes. The finding that the growth of clonogenic Molt-4 cells was almost completely abolished following treatment with interferon (IFN)-alpha rA in the dose of 10(3) U/ml, whereas growth of K-562 cells was only slightly affected by similar treatment, suggested that NK cells may mediate inhibition of clonogenic leukemias through various mechanisms.