Cholesterol is a critical cellular component for T-lymphocyte cytotoxicity.

Abstract

Preincubation of cytolytic T [thymus-derived] lymphocytes (CTL) generated in secondary C57BL/6 anti-DBA/2 mixed leukocyte cultures with an inhibitor of cellular cholesterol synthesis (25-OH-cholesterol) for 24 h strongly depressed the cytolytic activity as determined in a 3 h 51Cr assay. The effect of the inhibitor was reversed by the simultaneous addition of cholesterol or of mevalonic acid during the preincubation period (mevalonate is the product of the regulatory enzyme in the sterol synthesis pathway, 3-hydroxy-3-methylglutaryl-CoA reductase (NADP) [mevalonate:NADP+ oxidoreductase (CaA-acylating), EC 1.1.1.34]). Inhibition of DNA synthesis had no effect on CTL activity. The effect of 25-OH-cholesterol may be related to its inhibitory effect on sterol synthesis, resulting in decreased levels of membrane-bound cholesterol, rather than inhibition of cellular proliferation.