Cholesterol synthesis in polyclonally activated cytotoxic lymphocytes and its requirement for differentiation and proliferation.

The kinetics of sterol synthesis and DNA synthesis in polyclonally activated, concanavalin A-stimulated spleen cell cultures were analyzed. Inhibition of DNA synthesis by 1-beta-D-arabinofuranosylcytosine (Ara-C) did not abrogate the formation of cytotoxic effector cells. However, inhibition of sterol synthesis by 25-hydroxycholesterol inhibited formation of cytotoxic effector cells as well as cellular proliferation. The inhibition of cytotoxicity correlated well with the dose of 25-hydroxycholesterol administered and was dependent on the time of administration. The agent had to be present when sterol synthesis occurred normally during the time lapse before DNA synthesis began. Compactin had the same effect as 25-hydroxycholesterol. The effects of inhibition of sterol biosynthesis on cytotoxicity could be counteracted by addition of cholesterol-containing liposomes. Based on these experiments, the links between proliferation and differentiation in lymphocytes are discussed.