Membrane markers, target cell specificity, and sensitivity to biological response modifiers distinguish human natural cytotoxic from human natural killer cells.

In the present report, we provide evidence for the distinct existence of a human natural cytotoxic (HNC) cell. This HNC cell can be identified by the monoclonal antibody HNC-1A3 and by the absence of the T10 antigen, other antigenic markers being shared, at least in part, with natural killer (NK) cells, T cells, or monocytes. In addition, the HNC cell preferentially kills the MA-160 target, the herpes simplex virus-1-infected MA-160 cell line, and the two human tumor cell lines HEp-2 and HF-2. It has weak lytic activity against the NK-sensitive K562 cell line or its relatively NK-resistant clone I subline. The cytotoxic activity of the HNC cell is not augmented by interferon but is markedly enhanced by interleukin 2 and by a measles-virus-induced factor (MVF). Furthermore, it is not inhibited by cyclosporin A (CsA), in contrast to NK cell cytotoxicity against the K562 target cell line which is augmented by interferon, inhibited by CsA, and not affected by MVF. These data suggest that spontaneously cytotoxic cells may belong to more than one subset of human lymphocytes, and that HNC cells may be defined in man using membrane markers, target cell specificity, and sensitivity to biological response modifiers.