Characterization of HNK-1⁺ (Leu-7) human lymphocytes. II. Distinguishing phenotypic and functional properties of natural killer cells from activated NK-like cells

HNK-1⁺ and HNK-1^- lymphocytes from human blood were sorted with a fluorescence-activated cell sorter and compared for their phenotypic and functional properties. The HNK-1⁺ cells exhibited virtually no response to either mitogens (PHA, Con A, and PWM) or allogeneic cells, because the ³H-thymidine uptake for HNK-1⁺ cells was only 1 to 3% of that for HNK-1^- cells. On the other hand, the HNK-1^- cells responded efficiently to these stimuli and acquired a potent killing activity against K562 and other target cells after stimulation. The proliferating lymphoblasts did not acquire the HNK-1 antigen. These activated HNK-1^- cells had a wider spectrum of spontaneous cytotoxicity than did HNK-1⁺ cells against 12 different target cells. Two distinct populations of effector cells for spontaneous killing can thus be distinguished on the basis of HNK-1 antigen expression. The classically defined NK cells are HNK-1⁺, whereas effector cells activated by either mitogens or allogeneic cells are HNK-1^-. The HNK-1⁺ cells were not generated from the pool of HNK-1^- cells under any of the culture conditions tested. The NK cells defined by the HNK-1 antibody are thus a functionally distinct population of cells. Although some HNK-1⁺ cells may also express T cell-associated antigens and sheep erythrocyte receptors, they lack some important functional properties ascribed to T cells.