Hyperthermic inactivation, recovery and induced thermotolerance of human natural killer cell lytic function

Abstract

Natural killer (NK) cytotoxic activity in human peripheral blood mononuclear cells or preparations of large granular lymphocytes was assayed after a hyperthermia treatment. Human NK cells are very sensitive to hyperthermic inactivation; 30 min at 42°C reduced NK lytic activity toward K562 target cells by 40–50%, 43 °C by 85–90% and 44°C or 45°C by 100%, but similar treatment of the target cells did not alter their sensitivity to lysis. However, holding at 37°C allowed heated NK cells to recover their lytic activity. The extent of the recovery was inversely correlated with the temperature as well as the recovery time. Heated and subsequently recovered NK cells were more thermotolerant to loss of lytic function by a further hyperthermia exposure. About 0.65°C increase in temperature was required for a 50% loss of lysis ability in the NK cells made thermotolerant by a previous hyperthermic exposure at 43°C for 30 min. The V_max for NK lytic activity of cells heated at 42°C for 30 min was reduced by 70% compared with that of normal NK cells. When heated cells were incubated the V_max recovered. There are at least two heat-sensitive processes involved in NK cytotoxic activity. Cells completely inactivated for target cell lysis by a 44°C exposure still showed recognition and binding functions and acted as competitive inhibitors of unheated NK cells. Cells heated at 45°C caused less inhibition and had lower ability to recognize and bind target cells. The lytic function is therefore a more heat-sensitive process than the recognition and binding functions, but both are heat-inhibitable. Individual variations in thermal sensitivity, recovery and induced thermotolerance were evident.

Key Words:

• Hyperthermia
• human natural killer cells
• thermotolerance
• cytotoxic cells
• membranes