HEAT-TREATMENT OF LEUKEMIC-CELL LINES CAN INCREASE THEIR SENSITIVITY TO NK LYSIS

The effect of stress on target cell susceptibility to human natural ki ller cell-mediated lysis was examined. Targets were incubated at 37, 4 2, or 45 degrees C for 1 hr and then tested for NK sensitivity in chro mium-release assays, The T cell target JURKAT displayed minor increase s in susceptibility to NK lysis with 42 degrees C pretreatment (20-50% increases) and dramatic increases in lysability with 45 degrees C pre treatment (100-300% increase) compared to control, In contrast, lysis of the NK prototypic target K562 is not increased after 42 or 45 degre es C pretreatment, Kinetic studies indicated an optimal NK sensitivity enhancement time of 1 hr at 45 degrees C for JURKAT. Inhibition of ta rget cell protein synthesis by emetine pretreatment does not produce a n increase in susceptibility to NK lysis, JURKAT cells pretreated with sodium arsenite exhibited a comparable increase in NK sensitivity to the heat treatments, Cold target inhibition assays suggest that the in crease in sensitivity after heat treatment is at a postbinding stage, This was exemplified by the increased sensitivity of JURKAT, but not K 562, to lysis mediated by isolated rat NK granules, These results indi cate that a heat-sensitive, de novo protein synthesis-independent defe nse mechanism against lysis may exist in some tumors, altering their s usceptibility to lysis by NK cells. (C) 1995 Academic Press, Inc.