CD8^(+)Treg细胞在慢性鼻窦炎中的表达及其与嗜酸粒细胞浸润的研究  

Expression of CD8^(+)Treg cells in chronic rhinosinusitis and its correlation with eosinophilic infiltration

作　　者：常利红[1] 陈晓红[1] 李帅祥 李霞[1] 黄子真[1] 黄健聪[1] 张革化[1] Chang Lihong;Chen Xiaohong;Li Shuaixiang;Li Xia;Huang Zizhen;Huang Jiancong;Zhang Gehua(Department of Otorhinolaryngology,Head and Neck Surgery,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院耳鼻咽喉头颈外科,广州510630

出　　处：《中华耳鼻咽喉头颈外科杂志》2022年第2期142-152,共11页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：国家自然科学基金(82071020,81970859);高校基本科研业务费中山大学青年教师培育计划(19ykpy30);广州市科技计划项目(202002030034);广东省自然科学基金面上项目(2019A1515011093)。

摘　　要：目的明确CD8^(+)调节性T细胞(Treg细胞)在慢性鼻窦炎(CRS)患者鼻黏膜组织和外周血中的表达情况,及其与鼻黏膜组织中嗜酸粒细胞(Eos)浸润的关系。方法对2017年3月至2018年10月于中山大学附属第三医院的33例慢性鼻窦炎伴鼻息肉(CRSwNP)、26例慢性鼻窦炎不伴鼻息肉(CRSsNP)及27例对照组患者采集鼻黏膜组织及外周血,其中男59例,女27例,年龄18~72岁。苏木精-伊红染色检测鼻黏膜组织中Eos计数,将CRS患者分为嗜酸粒细胞性CRS(eosinophilic CRS,ECRS)和非嗜酸粒细胞性CRS(non-eosinophilic CRS,Non-ECRS)两组类型。采用流式细胞术检测各组患者鼻黏膜组织及外周血中CD4^(+)及CD8^(+)T细胞的比例、细胞毒性T细胞(cytotoxic T lymphocytes,Tc)1、Tc2及Tc17细胞的比例、CD8^(+)Foxp3^(+)和CD8^(+)Foxp3^(-)IL-10^(+)两种CD8^(+)Treg细胞的比例,以及产转化生长因子β(TGF-β)及白细胞介素(IL)-10的CD8^(+)Foxp3^(+)Treg细胞的比例。采用Graphpad 7.0进行作图,所有数据采用M(IQR)表示,采用SPSS 16.0软件进行统计学分析。结果CD8^(+)T细胞在所有患者鼻黏膜组织淋巴细胞中的比例高于CD4^(+)T细胞[37.75%(17.35%)比4.72%(4.29%),Z=-5.70,P<0.001],而在外周血淋巴细胞中的比例低于CD4^(+)T细胞[23.60%(9.33%)比44.05%(10.93%),t=9.72,P<0.001]。CRSwNP患者鼻黏膜组织中Tc2细胞和Tc17细胞比例显著高于CRSsNP患者及对照组[1.82%(1.22%)比0.84%(0.79%)比1.09%(0.92%),1.93%(2.32%)比0.54%(1.04%)比0.47%(0.51%),P值均<0.05]。与CRSsNP[0.43%(1.45%)]和对照组[0.48%(0.83%)]相比,CRSwNP患者鼻黏膜组织中CD8^(+)Foxp3^(+)Treg细胞占淋巴细胞比例最低[0.10%(0.32%),Z值分别为-2.24、-2.22,P值分别为0.025、0.027];CRSwNP患者鼻黏膜组织中产TGF-β和IL-10的CD8^(+)Foxp3^(+)Treg细胞占总CD8^(+)T细胞的比例显著低于对照组(Z值分别为1.46、0.49,P值均为0.001)。CRSwNP患者鼻黏膜组织中CD8^(+)Foxp3^(-)IL-10^(+)Treg细胞占总CD8^(+)T细胞的比例显著低于CRSsNP患�Objective To detect the percentages of CD8^(+)Treg cells in the nasal mucosa and peripheral blood of chronic rhinosinusitis(CRS)and to explore their correlation with eosinophilic infiltration.Methods Thirty-three chronic rhinosinusitis with polyp(CRSwNP),26 chronic rhinosinusitis without polyp(CRSsNP)and 27 control patients who were collected with the nose mucosal tissue and peripheral blood in the Third Affiliated Hospital of Sun Yat-sen University from March 2017 to October 2018 were selected,including 59 males and 27 females,aging from 18 to 72 years.Hematoxylin and eosin(HE)staining was used to observe the number of eosinophils in the nasal tissues and to classify the CRS into eosinophilic CRS(ECRS)and non-eosinophilic CRS(Non-ECRS).Flow cytometry was used to detect the percentages of CD4^(+)and CD8^(+)T cells in lymphocytes of nasal mucosa and peripheral blood.The percentages of CD8^(+)Foxp3^(+)Treg cells,CD8^(+)Foxp3^(-)IL-10^(+)Treg cells,CD8^(+)IFN-γ+T cells(Tc1),CD8^(+)IL-4^(+)T cells(Tc2)and CD8^(+)IL-17A+T cells(Tc17)in lymphocytes of nasal mucosa and peripheral blood were also tested.Besides,the percentages of Foxp3^(+)TGF-β+Treg cells and Foxp3^(+)IL-10^(+)Treg cells in CD8^(+)T cells were determined.All data were represented by M(IQR).GraphPad 7.0 and SPSS 16.0 were used for illustration and statistical analysis.Results The percentage of CD8^(+)T cells(37.75%(17.35%))was higher than that of CD4^(+)T cells(4.72%(4.29%))in nasal mucosa(Z=-5.70,P<0.001),while lower(23.60%(9.33%))than that of CD4^(+)T cells(44.05%(10.93%))in peripheral blood(t=9.72,P<0.001).CRSwNP patients possessed the highest Tc2(1.82%(1.22%))and Tc17(1.93%(2.32%))percentages than CRSsNP(Tc2:0.84%(0.79%);Tc17:0.54%(1.04%))and control(Tc2:1.09%(0.92%);Tc17:0.47%(0.51%),both P<0.05)patients.While,CRSwNP patients possessed the lowest CD8^(+)Foxp3^(+)Treg cells percentage(0.10%(0.32%))than CRSsNP(0.43%(1.45%))and control(0.48%(0.83%),Z value was-2.24,-2.22,respectively,P value was 0.025,0.027,respectively).The percentages of Foxp3^(+)TG

关 键 词：鼻窦炎 CD8^(+)Treg细胞 嗜酸粒细胞 

分 类 号：R765.41[医药卫生—耳鼻咽喉科]