慢阻肺小鼠肺组织CD8^(+)T细胞功能耗竭及抑制性受体阻断剂干预研究  

Study on CD8^(+)T cell exhaustion in lung tissue of mice with chronic obstructive pulmonary disease and the intervention of inhibitory receptor blocker

作　　者：陈宇鸣 李媛媛 庄虹[1] 丘国清 卓宋明[1] CHEN Yuming;LI Yuanyuan;ZHUANG Hong;QIU Guoqing;ZHUO Songming(Department of Respiratory and Critical Care Medicine,Shenzhen Longgang Central Hospital,Shenzhen,Guangdong 518116,China;State Key Laboratory of Respiratory Diseases,Guangzhou Medical University,Guangzhou,Guangdong 510000,China)

机构地区：[1]深圳市龙岗中心医院呼吸与危重症医学科,广东深圳518116 [2]广州医科大学呼吸疾病国家重点实验室,广东广州510000

出　　处：《临床肺科杂志》2024年第6期859-865,共7页Journal of Clinical Pulmonary Medicine

基　　金：深圳市龙岗区科技创新局(No.LGKCYLWS2020003)。

摘　　要：目的 初步探讨慢性阻塞性肺疾病小鼠CD8^(+)T细胞功能耗竭状态及抑制性受体抗体干预后变化。方法 将28只小鼠分为正常对照组、COPD对照组、PD-1抗体干预治疗组(COPD+Anti-PD-1组),以烟熏及LPS吸入方式建立COPD模型,PD-1抗体干预治疗组在造模12周后腹腔注射PD-1干预,16周后用小动物肺功能仪检测各组小鼠肺功能,流式细胞仪检测各组小鼠肺组织CD8^(+)T细胞PD-1表达水平及分泌细胞因子功能。留取小鼠部分肺组织行病理检查评估肺气肿程度。结果 COPD对照组CD8^(+)T细胞数量较正常对照组增多(P<0.01),COPD对照组表达PD-1的CD8^(+)T细胞较正常对照组增多(P<0.05),PD-1抗体干预治疗组CD8^(+)T细胞表达TNF-α比例较COPD对照组增多(P<0.01)。PD-1抗体干预治疗组小鼠气道阻力较COPD对照组小鼠下降(P<0.05)。PD-1抗体干预治疗组平均线性截距较COPD对照组下降(P<0.05),PD-1抗体干预治疗组平均肺泡数较COPD对照组增加(P<0.01)。结论 慢性阻塞性肺疾病小鼠肺组织CD8^(+)T细胞较正常对照组表达抑制性受体PD-1,存在功能耗竭,应用PD-1抗体治疗后可部分恢复CD8^(+)T细胞功能及改善肺功能。Objective To investigate CD8+T cell exhaustion in lung tissue of mice with chronic obstructive pulmonary disease and the changes after the intervention of inhibitory receptor antibody.Methods 28 mice were divided into the normal control group,the COPD control group,and the COPD+Anti-PD-1 group.COPD model was established by smoking and LPS inhalation,and the COPD+Anti-PD-1 group was intraperitoneally injected PD-112 weeks after modeling.The lung function of mice in each group was detected by small animal pulmonary function testing,and the expression level of PD-1 of CD8+T cells and the function of secreting cytokines in lung tissues were detected by flow cytometry.Part of lung tissues of mice were taken for pathological examination to evaluate the degree of emphysema.Results The number of CD8^(+)T cells in the COPD control group was higher than that in normal control group(P<0.01),PD-1 expression in the COPD control group was higher than that in the normal control group(P<0.05),and the proportion of CD8^(+)T cells expressing TNF-αin the COPD+Anti-PD-1 group was higher than that in the COPD control group(P<0.01).Airway resistance of mice in the COPD+Anti-PD-1 group was decreased compared with the COPD control group(P<0.05).The mean linear intercept of the COPD+Anti-PD-1 group was decreased compared with the COPD control group(P<0.05),and the mean alveolar number of the COPD+Anti-PD-1 groups was increased compared with the COPD control group(P<0.01).Conclusion CD8^(+)T cells in the lung tissue of mice with chronic obstructive pulmonary disease express more inhibitory receptors than those in the normal control group,showing CD8^(+)T cells exhaustion.PD-1 antibody treatment can partially restore the function of CD8^(+)T cells and improve lung function.

关 键 词：慢性阻塞性肺疾病 CD8^(+)T细胞耗竭 抑制性受体PD-1 

分 类 号：R563.9[医药卫生—呼吸系统]