Mechanism of cell-mediated cytotoxicity at the single cell level. IV. Natural killing and antibody-dependent cellular cytotoxicity can be mediated by the same human effector cell as determined by the two-target conjugate assay.

The present study examines the relationship between natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) in man. Although some reports have suggested that these cytotoxic activities are mediated by distinct subpopulations of effector cells, others have reported that the effector is the same. In the work presented here, we have resolved that NK cytotoxicity and ADCC can be mediated by the same effector cell. This is shown at both the population and single cell levels. At the single cell level, lines of evidence are presented that show unequivocally that the same effector cell can mediate both NK and ADCC reactions: 1) Large granular lymphocytes- (LGL) enriched cell fractions contain an increased frequency of target-binding effectors against NK and ADCC targets, as well as an increased number of cytotoxic cells. 2) Single lymphocytes in the LGL population simultaneously bind to both NK and ADCC targets, which reveals that single effectors have receptors for both targets. This finding is seen using the two-target conjugate assay, where a single effector cell binds to both a fluorescent NK target and a nonfluorescent ADCC target. 3) A significant number of lymphocytes in these mixed two-target conjugates kill both NK and ADCC targets. The frequency with which NK and ADCC targets are killed equals the frequency with which both targets are killed in a two-target conjugate consisting of two identical targets (two NK or two ADCC targets) or two nonidentical NK targets (K562 and Molt-4). These results indicate that a single effector cell is capable of first binding to, and then killing, both NK and ADCC targets, which reveals the existence of a multipotential cytotoxic effector system in man. Since NK and ADCC have been shown to be mediated by distinct recognition mechanisms, each of these receptor-target interactions appears to be able to trigger the delivery of a lethal hit from a single NK-ADCC effector cell.