Regulation of human natural killing by lysosomotropic and thiol-reactive agents.

Treatment of human peripheral blood lymphocytes (PBL) with ammonium or other lysosomotropic amines eliminates natural killing (NK) activity of effector cells without affecting their viability. Inhibition of NK by these reagents is probably due to blocking of events subsequent to effector cell target cell binding but before programming for cytolysis. Treatment of K562 target cells with the same reagents has no effect on target cell sensitivity to NK. Pretreatment of effector cells with the NK inhibitory lysosomotropic agents decreases lysosomal thiol cathepsin activity without affecting the lysosomal acid phosphatase activity. Thiol-reactive agents, tosyl-L-lysine chloromethyl ketone (TLCK) and iodoacetamide also inhibit NK and thiol cathepsin activity in PBL. These data suggest a role for thiol-containing enzymes in the early stages of NK cytolysis.