【摘要】 目的 研究 B、T 淋巴细胞衰减因子 （B and T lymphocyte attenuator,BTLA） 及其配体疱疹病毒进入中介体（herpesvirus entry mediator,HVEM）在肺结核患者 CD4⁺CD25⁺CD127^low调节性 T 细胞(CD4⁺CD25⁺CD127^lowTreg)中的表达及其与患者临床特征的关系。方法 选取肺结核患者 30 例（肺结核组）和 20 例健康体检者（健康对照组），通过流式细胞术检测 2 组外周血淋巴细胞 CD4⁺CD25⁺CD127^lowTreg 细胞的阳性率，以及检测 BTLA/HVEM 在肺结核患者外周血和淋巴细胞上的表达；利用蛋白芯片法检测结核抗体；通过影像检测结果判断肺结核进展程度；采用罗氏培养法培养结核分枝杆菌。结果结核组 CD4⁺CD25⁺CD127^lowTreg 所占比例为（9.14±2.66）%，健康对照组 CD4⁺CD25⁺CD127^lowTreg 所占比例为（6.39±1.73）%，相对于健康对照组，肺结核组患者外周血中 CD4⁺CD25⁺CD127^lowTreg 比率明显增高；健康对照组 CD4⁺CD25⁺CD127^lowTreg上 BTLA 和 HVEM 的表达率高于肺结核组；BTLA、HVEM 在肺结核组患者 CD4⁺CD25⁺CD127^lowTreg 上的表达呈正相关；BTLA、HVEM 在 CD4⁺CD25⁺CD127^lowTreg 上的表达在痰涂阳性患者组中更低，而与其他临床特征无关。结论 肺结核患者体内的 CD4⁺CD25⁺CD127^lowTreg 增高，可能是抗结核免疫应答被抑制的原因，提示过度扩增导致数量异常增高的 Treg 是免疫应答不足和 MTB 逃逸的一个重要因素。负性共刺激信号 BTLA/HVEM 在结核患者体内下调提示其参与对 CD4⁺CD25⁺CD-127^lowTreg 的增殖的抑制作用。更多还原

【Abstract】 Objective To study the negative costimulatory molecules B and T lymphocyte attenuator （BTLA） and its ligand herpesvirus entry mediator （HVEM） in CD4⁺CD25⁺CD127^lowregulatory T cells (CD4⁺CD25⁺CD127^lowTreg) of pulmonary tuberculosis patients and analyze the relationship between BTLA/HVEM expression and clinical characteristics. Methods Thirty patients with pulmonary tuberculosis （tuberculosis group） and 20 healthy people（healthy control group）were selected. The positive rate of CD4⁺CD25⁺CD127^lowTreg cells of both groups, as well as the expression of BTLA/HVEM in the peripheral blood and cells of pulmonary tuberculosis patients were detected with flow cytometry; the protein chip method was used to detect tuberculosis antibodies; the image detection results were used to judge the progress of tuberculosis; the Roche culture method was used to cultivate Mycobacterium tuberculosis. Results The proportion of CD4⁺CD25⁺CD127^lowTreg cells in the tuberculosis group was （9.14±2.66） %, and the proportion of CD4⁺CD25⁺CD127^lowTreg cells in the healthy control group was （6.39±1.73） %. Compared with the healthy control group, the ratio of CD4⁺CD25⁺CD127^lowTreg cells in the pulmonary tuberculosis group was significantly higher. The expression rate of BTLA and HVEM on CD4⁺CD25⁺CD127^lowTreg cells in pulmonary tuberculosis group was lower than that of the healthy control. The expressions of BTLA and HVEM were positively correlated. The expression of BTLA and HVEM on CD4⁺CD25⁺CD127^lowTreg cells was lower in the sputum smear-positive patient group, regardless of other clinical features. Conclusion The increase of CD4⁺CD25⁺CD127^lowTreg cells in pulmonary tuberculosis patients may be the cause for the suppression of anti-tuberculosis immune response, suggesting that excessive expansion leads to abnormally increased number of Tregs, which is an important factor for insufficient immune response and mycobacterium tuberculosis escape. The down-regulation of the negative costimulatory signal BTLA/HVEM in tuberculosis patients suggests its involvment in the inhibition of the proliferation of CD4⁺CD25⁺CD127^lowTreg cells.更多还原