Differential oncolytic effect of NK-enriched subsets in long-term interleukin-2 cultures

The aim of this study was to characterize the oncolytic efficacy of human natural killer (NK) cell subsets generated from highly NK-enriched population in long-term IL-2 cultures. NK cells cultured for 3 weeks with interleukin-2 (IL-2) were separated into several subsets using two color fluorescence-activated cell sorting and CD2, CD8, CD16, and CD56 monoclonal antibodies. These individual NK cell subsets were then tested for cytotoxicity against various tumor target cell lines, including K-562, Daudi, and Ovcar-3. The CD16+/CD56+ NK cell subset was superior in its cytotoxic activity against all targets in comparison to the CD16-/CD56+ subset. Within CD16 population, CD16+CD2+ NK cells were most potent; however CD16+/CD2- subset was also cytotoxic, indicating that CD2 molecule is important, but not necessary for NK cell cytotoxic function. CD16+/CD8+ and CD16+/CD8- subsets showed variance in cytolytic efficacy, depending on the tumor target tested. Highest cytotoxicity against K-562 was observed in the CD16+/CD8+ population, while the CD16+/CD8- subset manifested highest cytotoxic activity against Daudi. No significant differences within these NK cell subsets were observed against Ovcar-3 targets. These data indicate that NK cell subsets are not equally oncolytic, and that the oncolytic effect may be tumor dependent.