FoxP3^+CD4^+CD25^+调节性T细胞在重症肌无力发病机制中的作用

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

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FoxP3mRNA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FoxP3mRNA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FoxP3 mRNA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。

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 ioolymerase 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.