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
Bradley, T.P.; Bonavida, B.
Journal of Immunology 129(5): 2260-2265
The relationship between natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) in man was examined. 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. Here, it was 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. Large granular lymphocyte (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. 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 2-target conjugate assay, where a single effector cell binds to both a fluorescent NK target and a nonfluorescent ADCC target. A significant number of lymphocytes in these mixed 2-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 2-target conjugate consisting of 2 identical targets (2 NK or 2 ADCC targets) or 2 nonidentical NK targets (K562 and Molt-4 [human leukemia cells]). Apparently, 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 may be able to trigger the delivery of a lethal hit from a single NK-ADCC effector cell.