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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n U检验、皮尔逊相关性分析。n 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CD8n +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%)，n U＝23.500、43.500，n P＝0.000 8、0.020 5]和non-TB组[15.95%(12.46%)和45.30%(19.75%)，n U＝64.000、69.000，n P＝0.002 3、0.003 8]，差异均有统计学意义；硅沉着病患者外周血CD8n +T细胞上PD-1与TIGIT的表达呈正相关(n r＝0.434 3，n P<0.01)。APTB组患者外周血CD8n +T细胞上PD-1n +TIGITn +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-1n -TIGITn -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(n U＝76.500、41.000、58.000、41.000，n P＝0.007 1、0.015 4、0.001 3、0.015 4)。APTB组患者外周血CD8n +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(n U＝46.500、46.000，n P＝0.000 3、0.028 3)。T-bet的表达与TIGIT的表达呈正相关(n r＝0.456 7，n P<0.01)。APTB组患者外周血PD-1n +TIGITn +CD8n +T细胞亚群上T-bet[65.40%(12.12%)]的表达水平分别高于LTBI组[48.30%(28.75%)]和non-TB组[45.30%(19.75%)]，差异均有统计学意义(n U＝23.500、65.000，n P＝0.000 8、0.002 6)。n 结论:硅沉着病合并APTB患者外周血CD8n +T细胞上高表达免疫抑制受体PD-1和TIGIT，提示患者外周血CD8n +T细胞存在免疫耗竭现象，但T-bet的高表达又提示此耗竭细胞亚群具有一定的可逆转潜力。n “,”Objective: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 n Mycobacterium tuberculosis infection.n 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 n U test and Pearson correlations analysis were used for statistical analysis.n 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 CD8n + 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; n U=23.500 and 43.500, respectively, n P=0.000 8 and 0.020 5, respectively) and non-TB group (15.95%(12.46%) and 45.30%(19.75%), respectively; n U=64.000 and 69.000, respectively, n P=0.002 3 and 0.003 8, respectively), and the differences were all statistically significant. The expression of TIGIT was positively correlated with PD-1 on CD8n + T cells in silicosis patients (n r=0.434 3, n P<0.01). The proportion of PD-1n + TIGITn + CD8n + T cells in the APTB group (19.90%(22.67%)) was significantly higher than those in the non-TB group (11.55%(11.29%), n U=76.500, n P=0.007 1) and LTBI group (11.55%(10.53%), n U=41.000, n P=0.015 4), while the proportion of PD-1n -TIGITn -CD8n + T cells in the APTB group (30.60%(12.90%)) was significantly lower than non-TB group (48.90%(18.98%), n U=58.000, n P=0.001 3) and LTBI group (47.20%(24.59%), n U=41.000, n P=0.015 4). The differences were all statistically significant. The expression of T-bet on the peripheral blood CD8n + T cells in the APTB group (29.45%(16.78%)) was higher than that in the non-TB group (15.95%(12.46%)) and the LTBI group (17.40%(11.17%)), and the differences were both statistically significant (n U=46.500 and 46.000, respectively, n P=0.000 3 and 0.028 3, respectively). The expression of T-bet on CD8n + T cells was positively correlated with TIGIT on CD8n + T cells (n r=0.456 7, n P<0.01). The expression of T-bet on PD-1n + TIGITn + CD8n + T cells in the APTB group (65.40%(12.12%)) was higher than those in the LTBI group (48.30%(28.75%), n U=23.500, n P=0.000 8) and non-TB group (45.30%(19.75%), n U=65.000, n P=0.002 6), and the differences were both statistically significant.n Conclusion:The immunosuppressive receptor PD-1 and TIGIT are highly expressed on CD8n + T cells in silicosis patients with active pulmonary tuberculosis, which indicates CD8n + T cells exhaustion in these population, while the highly co-expression of T-bet suggests the exhausted subsets may have reversed potentiality.n