水仙环素抑制T细胞增殖的作用机制

目的探究水仙环素抑制T细胞增殖与功能的作用机制。方法密度梯度离心法及免疫磁珠法纯化人外周血T细胞,anti-CD3/anti-CD28抗体活化T细胞。使用流式细胞仪检测细胞增殖、CD25的表达、细胞毒性及细胞周期;酶联免疫吸附试验检测细胞因子IL-2、IL-6、IL^-17及IFN-γ的分泌水平。结果水仙环素抑制anti-CD3/anti-CD28抗体活化的T细胞增殖,IC₅₀为(0.011±0.001)μmol·L^-1,且浓度达0.24μmol·L^-1也不影响静息T细胞的存活。水仙环素抑制活化T细胞表达CD25和分泌IL-2,阻滞T细胞周期于G_0/G_1期。水仙环素对细胞因子IL-6、IL^-17及IFN-γ的抑制作用呈剂量依赖效应。结论水仙环素抑制T细胞增殖活化并显著抑制促炎细胞因子分泌,提示水仙环素有望成为先导化合物开发新型免疫抑制剂。

The mechanism of narciclasine inhibiting T cell proliferation

This study was performed to investigate the mechanism of narciclasine in inhibiting human T cell proliferation.Human peripheral blood T cells were purified by density gradient centrifugation and immunomagnetic microbeads,then activated by anti-CD3/anti-CD28 mAbs.Flow cytometry was used to measure the cell proliferation,cell cycle,CD25 expression and cytotoxicity of resting T cells,while ELISA assay was used to detect the secretion of cytokines IL-2,IL-6,IL^-17 and IFN-γ.Data showed that narciclasine inhibited the T cell proliferation activated by anti-CD3/anti-CD28 mAbs with an IC50 value of 0.011±0.001μmol·L^-1,but had no effect on resting T cells survival,even at the concentration up to 0.24μmol·L^-1.Narciclasine inhibited the expression of CD25 and IL-2 and induced T cell cycle arrest in G0/G1 phase.The inhibitory effects of narciclasine on IL-6,IL^-17 and IFN-γwere dose-dependent.In conclusion,narciclasine inhibits the proliferation and activation of T cells,and also significantly inhibits the secretion of pro-inflammatory cytokines,suggesting that narciclasine may be a potential lead compound for the development of new types of immunosuppressant.