Plasma membrane cholesterol regulates human lymphocyte cytotoxic function

Cell cholesterol is believed to be confined mainly to the plasma membrane. Treatment here of human peripheral blood lymphocytes with cholesterol-free and cholesterol-containing liposomes to effect, respectively, decreases or increases in cholesterol content measureable by chemical analysis, markedly altered effector functions of the cells. Depletion of cholesterol evoked inhibition of spontaneous and phytohemagglutinin-dependent lymphocyte cytotoxicity against allogeneic target cells. Opposite effects resulted from cholesterol enrichment, with PHA-dependent and antibody-dependent cytotoxicities increasing significantly. Treatment, instead, with the known inhibitor of cholesterol biosynthesis, 25-hydroxycholesterol, had suppressive effects like those resulting from lowering the cholesterol level physically by liposome treatment. Our data suggest that the plasma membrane cholesterol content of different categories of lymphocytes in man is both essential and regulatory for their cytotoxic function.