原发性胆汁性胆管炎患者CD8＋T细胞及FoxP3＋CD4＋T细胞中程序性死亡受体-1表达分析  

Expression of programmed death-1 in CD8＋ T lymphocyte and Treg lymphocyte in patients with primary biliary cholangitis

作　　者：张硕[1] 王立[1] 赵丽伶 孙金磊 陈志磊 邵体红[1] 陈华[1] 杨云娇[1] 李永哲[1] 张奉春[1] Zhang Shuo;Wang Li;Zhao Liling;Sun Jinlei;Chen Zhilei;Shao Tihong;Chen Hua;Yang Yunjiao;Li Yongzhe;Zhang Fengchun(Department of Rheumatology,Peking Union Medical College Hospital,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院风湿免疫科,100730

出　　处：《中华风湿病学杂志》2018年第8期532-536,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（81771764）;国家重点研发计划（2016YFA-010100）;国家自然科学基金青年项目（81501414）;首发科研专项青年项目（2016-4-40111）

摘　　要：目的研究原发性胆汁性胆管炎（PBC）患者CD8＋T细胞和FoxP3＋CD4＋T细胞表面程序性死亡受体（PD）-1表达情况。方法收集69例就诊于北京协和医院的PBC患者的外周血及临床资料，根据是否接受过治疗分为初治组和复诊组，在复诊组中根据治疗反应分为难治组和稳定组；同时收集58名健康对照外周血。采用流式细胞术检测PD-1在PBC患者CD8＋T细胞和FoxP3＋CD4＋T细胞的表达情况，应用独立样本t检验和Pearson相关性分析，探究各组间表达差异及其与临床指标相关性。结果69例PBC患者外周血CD8＋T细胞PD．1表达[（12±9）％]比健康对照[（20±12）％]降低（t=-3．687，P〈0．01），PBC患者调节性T细胞比例[（5．6±3．7）％]较健康对照[（7．4±2．4）％]下降（t=2．048，P〈0．01），且PD．1＋细胞占F0xP3＋CD4＋T细胞比例升高[（30±12）％]与[（26±8）％]（t=-2．858，P〈0．05）。未发现CD8＋T细胞及其PD-1表达、调节性T细胞比例与各项临床指标存在相关性（P〉0．05）。调节性T细胞的PD．1表达率与PBC全球评分之间呈负相关（r=-0．307，P〈0．05）。结论PBC患者外周血PD．1在CD8＋T细胞表达较健康人减少，且在难治组患者中下降更为显著；FoxP3＋CD4＋T细胞表面PD-1表达较健康人水平升高，与预后PBC全球评分存在负相关，提示PD-1／PD-L1通路参与PBC发病的免疫机制。Objective To investigate the expression of programmed death receptor-1 （PD-1） in CD8＋T cells and FoxP3＋CD4＋ cells in patients with primary biliary cholangitis （PBC）. Methods The peripheral blood and clinical data of 69 PBC patients in Peking Union Medical College Hospital and 58 health controls （HC） were collected. They were divided into initial treatment group and follow-up group according to whether they were treated or not. Patients in the treatment group were further divided into the refractory group and stable group according to treatment response. Flow cytometry was used to detect the expression of PD-1 in CD8＋ T cells and FoxP3＋CD4＋ cells. T-test and Person correlation analysis were used for data analysis. Results The PD-1 expression in peripheral blood mononuclear cells （PBMCs） of 69 PBC patients （12±9）% was lower than that of HC （20±12）% （t=-3.687, P〈0.01）. The percentage of PD-1＋ in FoxP3＋ CD4＋T cells was significantly increased in PBC （5.6±3.7）% than HC （7.4±2.4）% （t=2.048, P〈0.01）. The proportion of CD8＋T cells, PD-1 expression in CD8＋T cells and the proportion of FoxP3＋CD4＋ cells weren＇t correlated with clinical parameters （P〉0.05）. There was a negative correlation between the expression of PD-1 cells in FoxP3 ＋CD4＋ cells and GLOBE score （r=-0.307, P〈0.05）. Conclusion The expression of PD-1 in peripheral CD8＋T lymphocytes of PBC patients is lower than that of HC, and decreases more significantly in the refractory group. The expression of PD-1 on FoxP3＋CD4＋T cells is higher than that in HC, and is negatively correlated with the prognostic GLOBE score. It suggests that PD-1/PD-L1 pathway participates in the immune mechanism of PBC.

关 键 词：胆管炎 胆汁性 CD8+T淋巴细胞 调节性T淋巴细胞 程序性死亡受体-1 相关性分析 

分 类 号：R575.7[医药卫生—消化系统]