Effects of in vitro hyperthermia on human natural killer cells

The present study demonstrates that human natural killer (NK) cells isolated from peripheral blood of normal individuals are highly sensitive to hyperthermia. The effect was time and dose dependent, and treatment of peripheral blood lymphocytes at 42 degrees for 1 hr almost completely abolished NK activity. The effect was not a consequence of cell death since only a small decrease in cell viability was observed and the viability of density gradient fractions enriched for NK activity was normal. Analysis of NK activity at the single-cell level by application of a conjugation assay in agarose revealed that hyperthermia interfered with target cell binding as well as the lytic cycle. Attempts to rescue NK activity after hyperthermia treatment by incubation overnight with human alpha-interferon or activation in mixed leukocyte culture was unsuccessful, indicating that even pre-NK cells are heat sensitive. In contrast, the proliferative response to alloantigens in mixed leukocyte culture and to the T-cell mitogen concanavalin A was unaffected. Hyperthermia exposure of cytotoxic T-lymphocyte generated in mixed leukocyte culture immediately before assay against allogeneic blast cells strongly inhibited their activity. Some alterations in the kinetics of stimulation with the B-cell mitogen Staphylococcus aureus bacteria were observed after heat exposure although maximal stimulation was at control levels. Thus, NK cells, including their precursors, seem to be preferentially sensitive to hyperthermia among various lymphoid subclasses.