来氟米特对系统性红斑狼疮T淋巴细胞的免疫调节作用

Immunoregulatory effects of leflunomide on systemic lupus erythematosus of T-lymphocytes

目的探讨来氟米特(LEF)在体外对系统性红斑狼疮(SLE)患者外周血T淋巴细胞的免疫调节作用。方法在植物血凝素(PHA)刺激下,SLE患者外周血T淋巴细胞与不同浓度的LEF5、15、45μg/ml共培养。检测各组T淋巴细胞的增殖、凋亡情况,分析各组T淋巴细胞免疫表型CD152、CD28的表达以及各组T淋巴细胞的干扰素(IFN)γ、白细胞介素(IL)10、转化生长因子(TGF)β1 mRNA水平。结果在体外,LEF对由PHA诱导的SLE患者T淋巴细胞的增殖、凋亡均有抑制作用,且抑制作用与LEF呈剂量依赖性。LEF对T淋巴细胞CD152、CD28的表达无明显影响。LEF促进IL-10、TGF-β1 mRNA的表达,抑制IFN-γ mRNA的表达。结论 LEF可能通过减少T淋巴细胞凋亡、促进T淋巴细胞分泌IL-10、TGF-β1以及减少T淋巴细胞分泌IFN-γ来下调SLE的免疫反应。

Objective To investigate the immunoregulatory effects of leflunomide（LEF） in vitro on T-lymphocytes in patients with systemic lupus erythematosus（SLE）.Methods LEF （5,15,45 μg/ml） was added into wells containing lymphocytes（2×105） from SLE patients in the presence of phytohemagglutinin（PHA）.The proliferation and immunophenotypes（CD152,CD28）of T-lymphocytes were analyzed by flow cytometry.Apoptosis of T lymphocytes and the mRNA expression of interferon γ（IFN-γ）,interleukin-10（IL-10）,transforming growth factor-β1（TGF-β1） were observed.Results With the presence of LEF,peripheral T-lymphocytes of SLE patients showed a significant decrease of proliferation activity and apoptosis in a dose-dependent manner.No inhibitory effects on CD152 and CD28 of T-lymphocytes were observed.LEF promoted the mRNA expressions of IL-10 and TGF-β1 and inhibited the mRNA expression of IFN-γ.Conclusion LEF may down-regulate the immune response of SLE through decreasing the apoptosis,promoting secreations of IL-10 and TGF-β1 and reducing IFN-γ expression of peripheral T-lymphocytes.