负性共刺激分子BTLA/HVEM抑制肺结核患者CD4^(+)CD25^(+)CD127^(low)调节性T细胞增殖  

Negative costimulatory molecule BTLA/HVEM inhibits the proliferation of CD4^(+)CD25^(+)CD127^(low) regulatory T cells in pulmonary tuberculosis patients

作　　者：杨晨晨 如克亚木·阿不都沙拉木 戴凡超 甫拉提·热西提 徐茜 Yang Chenchen;Rukeyamu-Abdusaramu;Dai Fanchao;Pulati Rexiti;Xu Qian(Department of Basic Medicine,School of Health and Nursing,Wuxi Taihu University,Wuxi,214064;Department of Tuberculosis,the Eighth Affiliated Hospital of Xinjiang Medical University,Urumqi,830000;Department of Clinical Medicine,Guangxi Guilin Medical College,Guilin 54100;Xinjiang Department of Immunology,School of Basic Medical Sciences,Xinjiang Medical University,Urumqi,830011)

机构地区：[1]无锡太湖学院健康与护理学院基础医学教研室,无锡214064 [2]新疆医科大学第八附属医院结核一科,乌鲁木齐830000 [3]广西桂林医学院临床医学专业,桂林541000 [4]新疆医科大学基础医学院免疫学教研室,乌鲁木齐830011

出　　处：《中国组织化学与细胞化学杂志》2022年第1期29-36,43,共9页Chinese Journal of Histochemistry and Cytochemistry

基　　金：省部共建中亚高发病成因与防治国家重点实验室开放课题(SKL-HIDCA-2018-8);新疆维吾尔自治区自然科学基金(2017D01C223);江苏省青蓝工程资助项目;江苏省无锡市滨湖区科技局“滨湖之光”人才计划。

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^(low)Treg)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^(low)Treg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^(low)Treg所占比例为(9.14±2.66)%,健康对照组CD4^(+)CD25^(+)CD127^(low)Treg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^(low)Treg比率明显增高;健康对照组CD4^(+)CD25^(+)CD127^(low)Treg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^(low)Treg上的表达呈正相关;BTLA、HVEM在CD4^(+)CD25^(+)CD127^(low)Treg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^(low)Treg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^(+)CD127^(low)Treg的增殖的抑制作用。Objective To study the negative costimulatory molecules B and T lymphocyte attenuator(BTLA)and its ligand herpesvirus entry mediator(HVEM)in CD4^(+)CD25^(+)CD127^(low)regulatory T cells(CD4^(+)CD25^(+)CD127^(low)Treg)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^(low)Treg 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^(low)Treg cells in the tuberculosis group was(9.14±2.66)%,and the proportion of CD4^(+)CD25^(+)CD127^(low)Treg cells in the healthy control group was(6.39±1.73)%.Compared with the healthy control group,the ratio of CD4^(+)CD25^(+)CD127^(low)Treg cells in the pulmonary tuberculosis group was significantly higher.The expression rate of BTLA and HVEM on CD4^(+)CD25^(+)CD127^(low)Treg 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^(low)Treg cells was lower in the sputum smear-positive patient group,regardless of other clinical features.Conclusion The increase of CD4^(+)CD25^(+)CD127^(low)Treg 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

关 键 词：负性共刺激分子 B、T淋巴细胞衰减因子 疱疹病毒侵入介质 活动性肺结核 CD4^(+)CD25^(+)CD127^(low)调节性T细胞 

分 类 号：R521[医药卫生—内科学]