Generation of natural killer-like activity in mixed lymphocyte-tumor cell cultures. I. Role of HLA-DR antigens as stimulatory molecules.

A number of human lymphoid and non-lymphoid leukemic cell lines differing for expression of HLA-DR antigens were analyzed for the ability to induce natural killer(NK)-like activity and proliferation in lymphocytes from healthy donors. The ability to elicit the generation of NK-like activity in the responder lymphocytes varied greatly depending upon the type of antimitotic treatment (gamma-irradiation versus mitomycin C) received by the tumor cells prior to the start of the mixed cultures. By contrast, the induction of T-cell proliferation was positively correlated with the presence of DR molecules on the tumor cell lines. Nevertheless, DR- leukemic cells pretreated with the appropriate antimitotic agent did induce a proliferative response in the mixed cultures. T lymphocytes cultured without stimulator cells in spent medium containing high levels of cell-free DR antigens failed to undergo blastogenesis and proliferation, indicating that DR antigens can function as stimulatory molecules only when they are cell-associated.