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多耐药肺结核患者特异性细胞免疫失衡与调节性T细胞CD4+ CD25+ CD127low有关
作者:范任华1  向延根1  杨励1  刘艳科1  陈平圣2  尹柯1  许忆新1  封文军1  傅满姣1  吴佳玲1  王雷1  齐志强1  喻容1   
单位:1. 长沙市中心医院, 湖南 长沙 410004;
2. 东南大学 医学院, 江苏 南京 210009
关键词:调节性T细胞CD4+ CD25+ CD127low CD4+T细胞 CD8+T细胞 多耐药肺结核 
分类号:R521
出版年·卷·期(页码):2015·34·第四期(525-531)
摘要:

目的:探讨调节性T细胞CD4+ CD25+ CD127low、CD4+及CD8+T细胞在多耐药结核患者中的免疫调节作用。方法:采取30例健康体检者(HD)、30例非耐药初治肺结核(S-TB)患者及30例多耐药结核病(MDR-TB)患者2ml肝素抗凝外周静脉血,经CD3、CD4、CD8、CD25、CD127流式抗体标记后Beckman流式细胞仪计数各组CD4+ CD25+ CD127low、CD3+、CD4+、CD8+百分比含量,计算CD4/CD8值。结果:MDR-TB组CD4+ CD25+ CD127low调节性T细胞百分比含量明显高于HD组与S-TB组(P=0.000),MDR-TB组CD4+T细胞百分比含量明显低于HD组与S-TB组(P<0.05),MDR-TB组CD8+T细胞百分比含量与HD组与S-TB组相比明显上升(P<0.05),MDR-TB组CD4/CD8值明显低于HD组与S-TB组(P<0.001);线性回归分析发现:HD组中CD4+ CD25+ CD127low调节性T细胞百分比含量与CD3+、CD4+、CD8+T细胞及CD4/CD8值均无相关性(P>0.05),非耐药初治肺结核患者CD4+ CD25+ CD127low调节性T细胞百分比含量与CD3+、CD4+T细胞无相关性(P>0.05)、与CD8+T细胞存在正相关(r=0.419,P=0.011)、与CD4/CD8值存在负相关(r=-0.519,P=0.002),耐药结核病患者CD4+ CD25+ CD127low调节性T细胞百分比含量与CD3+T细胞无相关性(P>0.05)、与CD4+存在负相关(r=-0.476,P=0.004)、与CD8+T细胞存在正相关(r=0.638,P=0.000)、与CD4/CD8值存在负相关(r=-0.776,P=0.000)。结论:随着肺结核病程的发展,外周血中CD4+ CD25+ CD127low调节性T细胞逐渐上调,特异性细胞免疫水平下调,二者之间存在相关性,调节性T细胞可能通过抑制结核患者特异性细胞免疫应答来影响肺结核病的进程。

Objective: To study the role of CD4+ CD25+ CD127low regulatory T cells, CD4+ and CD8+T cells in patients with multidrug-resistant tuberculosis. Methods: 30 cases of healthy donors(HD),30 cases of patients with susceptible primary tuberculosis(S-TB),30 cases of patients with multidrug-resistant pulmonary tuberculosis (MDR-TB)were involved. 2ml of peripheral venous blood was injected into heparin anticoagulation tube, labeled with the monoclonal antibody of CD3, CD4, CD8, CD25 and CD127. The percentage of CD4+ CD25+ CD127low regulatory T cells, CD3+, CD4+and CD8+T cells was counted by using Beckman flow cytometry(FCM), and the calculation of CD4/CD8 was conducted. Results: The percentage of CD4+ CD25+ CD127low T cells in MDR-TB patients was significantly higher than that in the HD group and in the S-TB group(P=0.000), the percentage of CD4+T cells in MDR-TB group was significantly lower than that in the HD group and in the S-TB group(P<0.05), and the percentage of CD8+T cells in MDR-TB increased significantly compared with that in the HD group(P<0.05), the ratio of CD4/CD8 in MDR-TB group was significantly lower than that in the HD group and in the S-TB group(P<0.001). There was no correlation between the percentage of CD4+ CD25+ CD127low regulatory T cells and the percentage of CD3+, CD4+, CD8+and CD4/CD8 in HD by using the method of linear regression analysis(P>0.05). In drug-susceptible TB patients, there was no correlation between the percentage of CD4+ CD25+ CD127low regulatory T cells and the percentage of CD3+and CD4+(P>0.05), a positive correlation between the percentage of CD4+ CD25+ CD127low regulatory T cells and the percentage of CD8+(r=0.419,P=0.011), and a negative correlation between the percentage of CD4+ CD25+ CD127low regulatory T cells and CD4/CD8 ratio(r=-0.519,P=0.002). In MDR-TB patients, there was no correlation between the percentage of CD4+ CD25+ CD127low regulatory T cells and the percentage of CD3+(P>0.05), a positive correlation between the percentage of CD4+ CD25+ CD127low regulatory T cells and the percentage of CD8+(r=0.638,P=0.000), and a negative correlation between the percentage of CD4+ CD25+ CD127low regulatory T cells and the percentage of CD4+(r=-0.476,P=0.004) and CD4/CD8 ratio(r=-0.776,P=0.000). Conclusion: With the development of pulmonary tuberculosis, CD4+ CD25+ CD127low regulatory T cells gradually increase in the peripheral blood of pulmonary tuberculosis patients, and specific cellular immunity levels decline, there is a correlation in them, CD4+ CD25+ CD127low regulator T cells may inhibit specific cellular immune response in MDR-TB patients.

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