Heiniger H J, Brunner K T, Cerottini J C
Proc Natl Acad Sci U S A. 1978 Nov;75(11):5683-7. doi: 10.1073/pnas.75.11.5683.
Preincubation of cytolytic T lymphocytes (CTLs) generated in secondary C57BL/6 anti-DBA/2 mixed leukocyte cultures with an inhibitor of cellular cholesterol synthesis (25-OH-cholesterol) for 24 hr strongly depressed the cytolytic activity as determined in a 3-hr 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 (CoA-acylating), EC 1.1.1.34]). Because, under the same culture conditions, inhibition of DNA synthesis had no effect on CTL activity, the experiments suggest that the effect of 25-OH-cholesterol is related to its inhibitory effect on sterol synthesis, resulting in decreased levels of membrane-bound cholesterol, rather than to inhibition of cellular proliferation.
在二级C57BL/6抗DBA/2混合白细胞培养物中产生的细胞溶解性T淋巴细胞（CTL）与细胞胆固醇合成抑制剂（25-羟基胆固醇）预孵育24小时后，在3小时的51Cr测定中，其细胞溶解活性被强烈抑制。在预孵育期间同时添加胆固醇或甲羟戊酸可逆转抑制剂的作用（甲羟戊酸是固醇合成途径中调节酶3-羟基-3-甲基戊二酰辅酶A还原酶（NADP）[甲羟戊酸：NADP +氧化还原酶（辅酶A酰化），EC 1.1.1.34]的产物）。由于在相同培养条件下，DNA合成的抑制对CTL活性没有影响，这些实验表明25-羟基胆固醇的作用与其对固醇合成的抑制作用有关，导致膜结合胆固醇水平降低，而不是对细胞增殖的抑制。
