CD4+CD25+Foxp3+T淋巴细胞抑制耐药肺结核患者机体细胞免疫研究

目的了解耐药肺结核患者外周血中CD4+CD25+Foxp3+T淋巴细胞及其分泌的细胞因子转化生长因子β1（TGF β1）、白细胞介素-10（IL 10）的表达水平与非耐药肺结核患者和健康对照者的差异，并探讨其在抑制特异细胞免疫反应中的作用。方法应用流式细胞技术分别对30例健康成人（健康对照组）、39例非耐药肺结核患者（普通肺结核组）及35例耐药肺结核患者（耐药肺结核组）的外周血CD4+CD25+T淋巴细胞和CD4+CD25+Foxp3+T淋巴细胞表达水平进行检测；采用酶联免疫吸附试验（ELISA）检测不同组别人群外周血血清中TGF β1、IL 10水平。结果健康对照组成人外周血中CD4+CD25+T淋巴细胞和CD4+CD25+Foxp3+T淋巴细胞分别占CD4+细胞总数的(17.09±5.43)%和(0.78±0.88)%；普通肺结核组外周血中上述两种细胞分别占CD4+细胞总数的(22.12±3.43)%和(2.79±1.65)%；耐药肺结核组外周血上述两种细胞分别占CD4+细胞总数的(24.01±5.65)%和(4.51±1.47)%。耐药肺结核组外周血中CD4+CD25+T淋巴细胞所占CD4+T淋巴细胞的比例较普通肺结核组高，但差异无统计学意义(P＞0.05)；耐药肺结核组CD4+CD25+Foxp3+T淋巴细胞的比例明显高于健康对照组及普通肺结核组 (P＜0.05)，并且耐药肺结核组TGF β1［（4.15±1.39）ρ/ng·L-1］、IL 10［（872.17±269.75）μg/L］明显高于普通肺结核组［分别为（3.03±1.42）ρ/ng·L-1、（266.83±57.09）μg/L］和健康对照组［分别为（2.12±0.77）ρ/ng·L-1、（105.21±23.56）μg/L］ (P＜0.05)。结论CD4+CD25+Foxp3+T淋巴细胞可能削弱结核病患者机体免疫系统对感染结核分枝杆菌的清除作用，是导致结核病感染慢性化且出现耐药的原因之一； TGF β1、IL 10可能参与抑制机体细胞免疫，与耐药结核病的形成和严重程度有一定相关性。

Inhibition of cellular immune response by CD4+CD25+Foxp3+T lymphocyte in drug resistant tuberculosis patients

ObjectiveTo explore the difference in CD4＋CD25＋Foxp3＋T lymphocytes and their secretion of cytokines transforming growth factor-β1（TGF-β1） and interleukin-10 （IL-10）among drug resistant tuberculosis （DR-TB） patients, non-drug resistant tuberculosis（non-DR-TB） patients and healthy control subjects, and evaluate its role in the inhibition of specific cellular immune response.MethodsFlow cytometry was applied to detect the expression levels of peripheral blood CD4＋CD25＋T lymphocytes and CD4＋CD25＋Foxp3＋T lymphocytes in 30 healthy subjects（control group）, 39 non-DR-TB patients（non-DR-TB group） and 35 DR TB patients（DR-TB group） ; enzyme linked immunosorbent assay （ELISA） was used to detect TGF-β1 and IL-10 levels in peripheral blood in different groups.ResultsCD4＋CD25＋T and CD4＋CD25＋Foxp3＋T lymphocytes accounted for （17.09±5.43）% and （0.78±0.88）% respectively of total number of CD4＋T cells in the peripheral blood of control group, （22.12±3.43）% and （2.79±1.65）% respectively in non-DR-TB group, （24.01±5.65）% and （4.51±1.47）% respectively in DR-TB group. The percentage of CD25＋CD4＋T lymphocytes in CD4＋T lymphocytes in DR-TB group was higher than that of non-DR-TB group, but the difference was not significant（P〉0.05）; the percentage of CD4＋CD25＋Foxp3＋T lymphocytes in CD4＋T lymphocytes in DR TB group was significantly higher than control and non-DR-TB group （P〈0.05）, and levels of TGF-β1（[4.15±1.39]ρ/ng·L-1） and IL-10（[872.17±269.75]μg/L） were significantly higher than those of non-DR-TB group （[3.03±1.42]ρ/ng·L-1 and [266.83±57.09]μg/L, respectively） as well as control group （[2.12±0.77]ρ/ng·L-1 and [105.21±23.56]μg/L, respectively） （P〈0.05）.ConclusionCD4＋CD25＋Foxp3＋T lymphocytes may weaken elimination funtion of immune system on Mycobacterium tuberculosis in TB patients,and related to the progress of tuberculosis infection as well as multidrug resistance. TGF-β1 and IL-10 may be involved in the inhibition of cellular immunity and have some correlation with the formation and the severity of the DR-TB.