Woerly G, Brooks N, Ryffel B
Institute of Pathology, University of Basel, Switzerland.
Clin Exp Immunol. 1996 Feb;103(2):322-7. doi: 10.1046/j.1365-2249.1996.d01-616.x.
The immunosuppressive macrolide rapamycin inhibits cytokine-driven proliferation of lymphocytes, acting at a later stage of T lymphocyte activation than the related compound FK506 or cyclosporin, which block IL-2 transcription. However, the effect of rapamycin on the expression of the IL-2 receptor alpha-chain (CD25) is less well documented. This study has investigated the effect of rapamycin on mRNA levels of CD25 and membrane expression of IL-2 receptor in human primary T lymphocytes activated by various stimuli. Rapamycin surprisingly inhibits CD25 upregulation subsequent to anti-CD3 or ionomycin stimulation. These effects are not secondary to an IL-2-mediated CD25 up-regulation, as rapamycin inhibits neither IL-2 synthesis nor IL-2-induced CD25 mRNA. Interestingly, sensitivity to rapamycin correlates with the requirement of de novo protein synthesis, as demonstrated by anisomycin inhibition of both ionomycin- and CD3-induced CD25 transcription. Thus, rapamycin inhibition of T cell activation may involve not only IL-2-driven proliferation, but also suppression of CD25 up-regulation.
免疫抑制性大环内酯类药物雷帕霉素可抑制细胞因子驱动的淋巴细胞增殖，其作用于T淋巴细胞激活的阶段比相关化合物FK506或环孢素更靠后，后者可阻断白细胞介素-2（IL-2）转录。然而，雷帕霉素对IL-2受体α链（CD25）表达的影响尚无充分记载。本研究调查了雷帕霉素对多种刺激激活的人原代T淋巴细胞中CD25的mRNA水平及IL-2受体膜表达的影响。雷帕霉素出人意料地抑制了抗CD3或离子霉素刺激后CD25的上调。这些作用并非继发于IL-2介导的CD25上调，因为雷帕霉素既不抑制IL-2合成，也不抑制IL-2诱导的CD25 mRNA。有趣的是，对雷帕霉素的敏感性与从头合成蛋白质的需求相关，这一点由茴香霉素对离子霉素和CD3诱导的CD25转录的抑制所证明。因此，雷帕霉素对T细胞激活的抑制可能不仅涉及IL-2驱动的增殖，还涉及对CD25上调的抑制。
