T细胞免疫球蛋白黏蛋白分子在活动性肺结核患者中的表达

Expressions of T-cell immunoglobulin and mucin domain molecules in peripheral blood of patients with active tuberculosis

目的探讨活动性肺结核患者外周血T淋巴细胞亚群、T细胞免疫球蛋白黏蛋白分子(T-cell immunoglobulin and mucin domain molecule,TIM)-1及TIM-3、细胞因子的变化。方法纳入2017年12月至2018年12月在浙江省中西医结合医院就诊和治愈的肺结核患者各50例,分成结核病组和结核病治愈组;另选同期在浙江省中西医结合医院进行体格检查的50名健康者,作为健康对照组。采用流式细胞术检测纳入对象的外周血T淋巴细胞亚群。采用实时荧光定量聚合酶链反应检测外周血单个核细胞中TIM-1、TIM-3、γ干扰素和白细胞介素(interleukin,IL)-4的mRNA水平。统计学方法采用t检验。结果结核病组CD4+T淋巴细胞/CD8+T淋巴细胞比值为1.21±0.50,分别低于结核病治愈组的1.88±0.62和健康对照组的1.92±0.82,差异均有统计学意义(t=2.148、2.207,均P<0.05)。结核病组TIM-1、TIM-3、IL-4的mRNA水平分别为2.16±0.37、1.59±0.36、1.52±0.69,分别高于结核病治愈组的1.60±1.23、1.01±0.52、0.91±0.36和健康对照组的1.40±0.27、0.92±0.34、0.79±0.42,差异均有统计学意义(结核病组比结核病治愈组t=14.120、11.440、17.730,结核病组比健康对照组t=12.090、12.050、17.030;均P<0.05);结核病组γ干扰素的mRNA水平为0.43±0.11,低于结核病治愈组的1.74±0.72和健康对照组的1.82±1.17,差异均有统计学意义(t=13.880、11.430,均P<0.05)。结论活动性肺结核患者的免疫功能紊乱可能与其体内CD4+T淋巴细胞/CD8+T淋巴细胞比值低下、TIM-1和TIM-3表达水平升高,以及辅助性T淋巴细胞(helper T lymphocyte,Th)1/Th2细胞因子比例失调有关。

Objective To investigate the changes of T-lymphocyte subsets,T-cell immunoglobulin and mucin domain molecule-1(TIM-1)and TIM-3 levels,and cytokines in the peripheral blood of patients with active tuberculosis.Methods From December 2017 to December 2018,50 tuberculosis patients and 50 cured tuberculosis patients in Zhejiang Hospital of Integrated Chinese and Western Medicine were selected as the tuberculosis group and cured tuberculosis group,respectively.Fifty healthy individuals in the same period were selected as the control group.Flow cytometry was used to detect the T-lymphocyte subsets in the peripheral blood.The mRNA levels of TIM-1,TIM-3,interferon(IFN)-γand interleukin(IL)-4 in peripheral blood mononuclear cells(PBMC)were detected by quantitative real-time polymerase chain reacticn(PCR).T test was used for statistical analysis.Results The ratio of CD4+/CD8+T lymphocytes in the tuberculosis group(1.21±0.50)decreased significantly,comparing with those in the cured tuberculosis group(1.88±0.62)and the control group(1.92±0.82).The differences were statistically significant(t=2.148 and 2.207,respectively,both P<0.05).The mRNA levels of TIM-1,TIM-3 and IL-4 in PBMC in the tuberculosis group were 2.16±0.37,1.59±0.36 and 1.52±0.69,respectively,which were all higher than those in the cured tuberculosis group(1.60±1.23,1.01±0.52 and 0.91±0.36,respectively)and the healthy control group(1.40±0.27,0.92±0.34 and 0.79±0.42,respectively).All of these differences were statistically significant(t=14.120,11.440,17.130,12.090,12.050 and 17.030,respectively,all P<0.05).However,the IFN-γmRNA level(0.43±0.11)was lower than that in the cured tuberculosis group(1.74±0.72)and the control group(1.82±1.17),and the differences were both statistically significant(t=13.880 and 11.430,respectively,both P<0.05).Conclusion The immune dysfunction in patients with active tuberculosis may be related to the low ratio of CD4+/CD8+T lymphocytes,the increased expressions of TIM-1 and TIM-3,and the imbalance of helper T lymphocyte(Th)1/Th2 cytokines.