多发性硬化患者外周血CD4^＋CD25^＋ T细胞变化及其机制探讨

Changes of CD4+CD25+ T Cells in Peripheral Blood of Multiple Sclerosis Patients and Possible Immunologic Mechanism

目的探讨多发性硬化(MS)患者外周血CD4+CD25+T细胞数量及叉头样转录因子(FOXP3)表达水平与MS病情的关系。方法选择温州地区MS患者44例(男12例、女32例),均按Poser诊断标准诊断,结合头颅MRI增强扫描排除合并其他神经系统和免疫系统疾病,并统一行EDSS评分;对照组43例(男13例、女30例)为健康查体者。具体方法:流式细胞仪检测外周血CD4+CD25+T细胞数量;免疫磁珠法分离CD4+CD25+T细胞;RT-PCR法检测CD4+CD25+T细胞FOXP3 mRNA表达并进行半定量分析。结果MS患者外周血中CD4+CD25+调节性T细胞数量与对照组比较无明显变化(P>0.05);活化的效应性T细胞数量增加(P<0.05)且活动期增加更为显著(P<0.01)。同一个体疾病活动期外周血CD4+CD25+调节性T细胞数量较非活动期减少(P<0.05)。MS患者外周血中CD4+CD25+T细胞的FOXP3 mRNA表达降低(P<0.05),且活动期降低更明显(P<0.01)。结论此组MS患者外周血CD4+CD25+调节性T细胞抑制活性降低,FOXP3 mRNA表达减少,活化的效应性T细胞数量增加,且与MS疾病活动性有关。

Objective To investigate the percentages of CD4^＋ CD25^＋ T cells in peripheral blood of patients with multiple sclerosis （MS）, and the relation between clinical data and the expression of transcription ：factor forkhead box P3（FOXP3） in CD4^＋CD25^＋ T cells. Methods Forty-four patients（12 males and 32 females） were collected into the study. Magnetic resonance imaging （MRI） and Poser diagnostic criteria were used to exclude the possibility of other nervous and immune system diseases. Clinical severity was scored by Kurtzke Expanded Disability Status Score（EDSS）. 43 healthy individuals（13 males and 30 females） served as controls. CD4^＋ CD25^＋ T cells were counted through flow cytometry. Then CD4^＋ CD25^＋ T cells were isolated through magnetic associated cell sorting（MACS）. Levels of FOXP3 expression were tested by RT--PCR. Results There were no significant differences between MS patients and healthy individuals as to the percentage of CD4^＋ CD25^＋ regulatory T cells（P〈0.05）. The percentages of effector T cells were significantly increased（P〈0.05） in MS patients, and more of them at the active stage（P〈0.01）. The percentage of CD4^＋ CD25^＋ regulatory T cells decreased in active MS patients and that of effector T cells increased when compared with inactive MS patient oneself（P〈0.05）. The levels of FOXP3 mRNA expression in CD4^＋ CD25^＋ T cells were decreased in MS patients （P〈0.05） ,especially at the active stage（P〈0.01 ）. Conclusions The immunosuppressive ability of CD4^＋ CD25^＋ regulatory T cells decreased in active MS patients. Levels of FOXP3 mRNA expression in CD4^＋ CD25^＋ T cells were lower. The percentage of effector T cells increased and it was related to disease activity.