免疫抑制受体T细胞免疫球蛋白和免疫受体酪氨酸抑制性基序结构域在硅沉着病合并结核分枝杆菌感染人群CD8^(+)T细胞中的表达  

Expression of immunosuppressive receptor T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain on CD8^(+)T cells in silicosis patients with Mycobacterium tuberculosis infection

作　　者：许毓贞 林淼垚 周晶雨 刘倩倩 杨清銮 林思然 邵凌云 张文宏 李立鸿 黄希田 张云桂[3] 阮巧玲 Xu Yuzhen;Lin Miaoyao;Zhou Jingyu;Liu Qianqian;Yang Qingluan;Lin Siran;Shao Lingyun;Zhang Wenhong;Li Lihong;Huang Xitian;Zhang Yungui;Ruan Qiaoling(Department of Infectious Diseases,Huashan Hospital,Fudan University,Shanghai 200040,China;Department of Infectious Diseases,The First People′s Hospital of Wenling,Wenling City 317500,Zhejiang Province,China;Department of Tuberculosis,Infectious Diseases Hospital Affiliated to Kunming Medical University,Kunming 650301,China)

机构地区：[1]复旦大学附属华山医院感染科,上海200040 [2]温岭市第一人民医院感染科,浙江省317500 [3]昆明医科大学附属传染病医院结核科,650301

出　　处：《中华传染病杂志》2021年第11期670-675,共6页Chinese Journal of Infectious Diseases

基　　金：国家自然科学基金(81801975);上海市青年科技英才扬帆计划(18YF1402800);云南省教育厅科学研究基金项目(2018JS251)。

摘　　要：目的探讨免疫抑制受体T细胞免疫球蛋白和免疫受体酪氨酸抑制性基序结构域(T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain,TIGIT)在硅沉着病合并结核分枝杆菌感染人群外周血单个核细胞上的表达及临床意义。方法2018年8月,纳入78例硅沉着病患者,均为浙江省三门县采石矿工人,分为硅沉着病合并活动性肺结核(active pulmonary tuberculosis,APTB)组(以下简称APTB组)、硅沉着病合并结核潜伏感染(latent tuberculosis infection,LTBI)组(以下简称LTBI组)和单纯硅沉着病无结核感染(non-tuberculosis infection,non-TB)组(以下简称non-TB组)。应用流式细胞术检测患者外周血单个核细胞中TIGIT、程序性死亡蛋白-1(programmed death-1,PD-1)和转录因子T-bet的表达水平。统计学分析采用曼-惠特尼U检验、皮尔逊相关性分析。结果78例患者中,APTB组8例,LTBI组24例,non-TB组46例。APTB组患者外周血CD8^(+)T细胞上PD-1和TIGIT[29.45%(16.78%)和65.40%(12.12%)]的表达水平分别高于LTBI组[17.40%(11.17%)和48.30%(28.75%),U=23.500、43.500,P=0.0008、0.0205]和non-TB组[15.95%(12.46%)和45.30%(19.75%),U=64.000、69.000,P=0.0023、0.0038],差异均有统计学意义;硅沉着病患者外周血CD8^(+)T细胞上PD-1与TIGIT的表达呈正相关(r=0.4343,P<0.01)。APTB组患者外周血CD8^(+)T细胞上PD-1+TIGIT+细胞亚群的表达[19.90%(22.67%)]高于non-TB组[11.55%(11.29%)]和LTBI组[11.55%(10.53%)],PD-1-TIGIT-细胞亚群[30.60%(12.90%)]的表达低于non-TB组[48.90%(18.98%)]和LTBI组[47.20%(24.95%)],差异均有统计学意义(U=76.500、41.000、58.000、41.000,P=0.0071、0.0154、0.0013、0.0154)。APTB组患者外周血CD8^(+)T细胞上T-bet[29.45%(16.78%)]的表达高于non-TB组[15.95%(12.46%)]和LTBI组[17.40%(11.17%)],差异均有统计学意义(U=46.500、46.000,P=0.0003、0.0283)。T-bet的表达与TIGIT的表达呈正相关(r=0.4567,P<0.01)。APTB组患者外周血PD-1+TIGIT+CD8^(+)T细胞亚群上T-bet[65.40%(12.12Objective To explore the expression and clinical significance of immunosuppressive receptor T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)on the peripheral blood mononuclear cells(PBMC)in silicosis patients with Mycobacterium tuberculosis infection.Methods August 2018,a total of 78 patients with silicosis(all were quarry workers in Sanmen County,Zhejiang Province)were enrolled and divided into silicosis combined with active pulmonary tuberculosis group(APTB group),silicosis combined with latent tuberculosis infection group(LTBI group),and simple silicosis with non-tuberculosis infection group(non-TB group).Flow cytometry was used to analyze the expressions of TIGIT,programmed death-1(PD-1)and transcription factor T-bet on PBMC from patients.Mann-Whitney U test and Pearson correlations analysis were used for statistical analysis.Results Among the 78 patients,eight were in the APTB group,24 in the LTBI group,and 46 in the non-TB group.The expressions of PD-1 and TIGIT on CD8^(+)T cells in the APTB group(29.45%(16.78%)and 65.40%(12.12%),respectively)were significantly higher than those in the LTBI group(17.40%(11.17%)and 48.30%(28.75%),respectively;U=23.500 and 43.500,respectively,P=0.0008 and 0.0205,respectively)and non-TB group(15.95%(12.46%)and 45.30%(19.75%),respectively;U=64.000 and 69.000,respectively,P=0.0023 and 0.0038,respectively),and the differences were all statistically significant.The expression of TIGIT was positively correlated with PD-1 on CD8^(+)T cells in silicosis patients(r=0.4343,P<0.01).The proportion of PD-1+TIGIT+CD8^(+)T cells in the APTB group(19.90%(22.67%))was significantly higher than those in the non-TB group(11.55%(11.29%),U=76.500,P=0.0071)and LTBI group(11.55%(10.53%),U=41.000,P=0.0154),while the proportion of PD-1-TIGIT-CD8^(+)T cells in the APTB group(30.60%(12.90%))was significantly lower than non-TB group(48.90%(18.98%),U=58.000,P=0.0013)and LTBI group(47.20%(24.59%),U=41.000,P=0.0154).The differences were all statistically significant.The

关 键 词：矽肺 结核 肺 T细胞耗竭 TIGIT 程序性死亡蛋白-1 T-BET 

分 类 号：R392[医药卫生—免疫学]