FoxP3+ CD4+ CD25+调节性T细胞在重症肌无力发病机制中的作用

目的 在细胞与分子水平检验重症肌无力(myasthenia gravis,MG)患者外周血中CD4+CD25+调节性T细胞(CD4+CD25+Tregs)的表达缺陷,探讨CD4+CD25+Tregs亚群异常与MG发病间的关系.方法 流式细胞技术检测21例MG患者(11例经胸腺切除)与20名健康对照者(healthy controls,HCs)外周血CD4+CD25+Tregs及FoxP3+CD4+CD25+Tregs含量,实时荧光定量聚合酶链反应(RT-FQ-PCR)分析MG患者与HCs外周血CD4+CD25+Tregs中FoxP3 mRNA的表达.结果 MG患者外周血CD4+CD25+ Tregs占CD4+T细胞含量与HCs比较无统计学差异(P＞0.05).MG患者外周血FoxP3+CD4+CD25+ Tregs含量及FoxP3 mRNA表达量与HCs比较均显著性降低(P＜0.05);胸腺切除的MG患者与未经胸腺切除的MG患者外周血FoxP3+CD4+CD25+ Tregs含量及FoxP3mRNA表达量无统计学差异(P＞0.05).结论 MG患者外周血CD4+CD25+ Tregs数量正常,但其表面分子FoxP3的表达下调,这种CD4+CD25+ Tregs亚群的异常发现有助于深入阐明MG的免疫发病机制.

The role of FoxP3+ CD4+ CD25+ T cells in the pathogenesis of myasthenia gravis

Objective To identify the expression defects of CD4+CD25+ regulatory T cells(CD4+CD25+ Tregs)in peripheral blood from myasthenia gravis(MG)patients at the cellular and molecular levels,with special focus on the effect of thymectomy on CD4+CD25+ Tregs,and to investigate the relationship between the abnormalities of CD4+CD25+ Tregs subset and the onset of MG.Methods Peripheral blood samples were obtained from 21 MG patients(11 patients have been thymectomized)and 20 healthy controls(HCs),flow cytometry was used to analyze the number of CD4+CD25+ Tregs and FoxP3+CD4+CD25+ Tregs and real-time fluorescent quantitative polymerase chain reaction(RT-FQ-PCR)was used to determine the FoxP3 mRNA level of CD4+CD25+ Tregs.Results There were no differences in the percentages of CD4+CD25+ Tregs among CD4+ T cells between MG patients and HCs(P>0.05),the FoxP3-positive CD4+CD25+ Tregs(FoxP3+CD4+CD25+ Tregs)and the mRNA expression of FoxP3 were significantly different in CD4+CD25+ Tregs of MG patients as compared to HCs(P<0.05);the frequencies of CD4+CD25+ Tregs and the expression of FoxP3 were similar in MG patients irrespective of treatment with thymectomy(P>0.05).Conclusions The number of the CD4+CD25+ Tregs is normal in MG patients,but the expression of their surface molecule Foxp3 is decreased.The abnormal finding on the CD4+CD25+ Tregs subset could contribute to further elucidate the immunologic pathogenesis in MG.