蛋白酶体抑制剂对T淋巴细胞增殖活化的影响

目的：探讨蛋白酶体（proteasome）抑制剂LAC（lactacystin）和β-LAC（β-lactacystin）对外周血T淋巴细胞增殖、活化的影响。方法： 以植物血凝素（phytohemagglutinin，PHA）作为刺激剂，经流式细胞仪检测T淋巴细胞增殖（BrdU掺入率），检测CD3+CD25+/CD3+及CD3+CD69+/CD3+细胞比例, 同时用RT-PCR检测蛋白酶体11S调节蛋白PA28及细胞因子IL-2 mRNA的表达。结果： （1）对预先活化的T淋巴细胞，LAC和β-LAC降低 T淋巴细胞BrdU掺入率（P＜0.05）；（2）LAC和β-LAC不影响T淋巴细胞CD69的表达（各时点，P＞0.05），而显著抑制T细胞表面抗原CD25表达（48 h、72 h，P＜0.05）；（3）与对照组相比，LAC和β-LAC明显下调T淋巴细胞PA28、IL-2 mRNA的表达(48 h、72 h，P＜0.05)。结论： LAC和β-LAC能够显著抑制T淋巴细胞增殖，这一效应与其抑制T淋巴细胞表面早期活化抗原CD25表达,下调PA28、IL-2 mRNA的表达有关。

Effect of lactacystin and β-lactacystin on the activation and proliferation of T-lymphocytes

AIM: To evaluate the effects of lactacystin (LAC) and β-lactacystin (β-LAC), proteasome inhibitor, on the proliferation and activation of T lymphocytes. METHODS: Flow cytometry was used to analyse the proliferation and the expression of CD69, CD25 and CD3 in PHA activated T-lymphocytes. Furthermore, the expression of PA28 and IL-2 mRNA were assayed by competitive RT-PCR. RESULTS: (1) LAC and β-LAC significantly decreased the incorporation in PHA activated T-lymphocytes. (2) Although LAC and β-LAC did not affect the expression of CD69 at any time, they significantly inhibited the expression of CD25 (48 h, 72 h, P＜0.05). (3) In comparison with control, LAC and β-LAC significantly down-regulated the expression of PA28 and IL-2 mRNA (48 h, 72 h, P＜0.05).CONCLUSIONS: LAC and β-LAC significantly inhibit the proliferation and activation of T lymphocytes. Mechanisms involved are inhibition of CD25 and down-regulation of PA28 and IL-2 mRNA expression.