慢性乙型肝炎患者外周血CD8^+T细胞亚群分布和PD-1表达特征研究  

Phenotypic distribution of circulating CD8^+T cells and characteristics of PD-1 expression on their subsets in chronic hepatitis B patients

作　　者：高见[1] 王喜红[2] 沈弢[1] 段昭君[1] 黄向博 鲁凤民[1] 

机构地区：[1]北京大学医学部基础医学院病原生物学系和感染病中心,北京100191 [2]山西省太原市第三人民医院,山西太原030012

出　　处：《中国病毒病杂志》2014年第4期293-298,共6页Chinese Journal of Viral Diseases

基　　金：国家"十二五"艾滋病和病毒性肝炎等重大传染病防治科技重大专项(2012ZX10002003;2012ZX10002005);北京市自然科学基金面上项目(7122108)

摘　　要：目的分析慢性乙型肝炎(CHB)患者外周血中CD8+T细胞及其亚群表面程序性死亡受体-1(PD-1)表达的变化特征及其临床关联性。方法用流式细胞术检测14例CHB患者和15例健康对照者外周血中CD8+T细胞及其亚群初始T细胞(TN)、中央记忆T细胞(TCM)、效应记忆T细胞(TEM)、终末效应记忆T细胞(TEMRA)的频数及细胞表面PD-1的表达水平,同时收集患者一般资料、生化指标和乙型肝炎病毒(HBV)病毒学指标等临床资料。使用SAS 9.1统计软件分析数据,应用Mann-Whitney U test分析组间差异,应用Spearman秩相关进行相关性分析,P<0.05为差异有统计学意义。结果与健康对照组相比,CHB患者的TEMRA亚群在CD8+T细胞中的频数显著降低(P=0.012),总CD8+T细胞(P=0.018)及其TEM亚群(P=0.004)表面PD-1的表达水平显著上升。相关性研究显示,CD8+TEM细胞表面PD-1的表达水平与HBV DNA载量呈显著正相关(r=0.554,P=0.040)。结论 CHB患者外周血中PD-1阳性的CD8+TEM频数升高,且与外周血中HBV DNA载量呈正相关,提示慢性乙型肝炎患者机体内HBV复制的活跃性可能与外周血中CD8+T细胞的活化状态,特别是其TEM亚群上PD-1的高表达关联。Objective To explore the frequencies and membrane molecule programmed death 1（PD-1）expression levels on peripheral CD8＋T cells and their corresponding naive subset（TN）,central memory subset（TCM）,effector memory subset（TEM）and terminal effector memory subset（TEMRA）,as well as their clinical correlations in chronic hepatitis B（CHB）patients.Methods Peripheral blood mononuclear cells（PBMC）were isolated from 14 CHB patients and 15 healthy donors.The frequencies and PD-1expression on total CD8＋T cells and their subsets（TN,TCM,TEMand TEMRA）were detected using multi-color flow cytometry.Sex,age and relevant clinical features of all enrolled participants were collected.The correlation of cell frequencies,PD-1expressions and clinical features were further investigated.Statistical analyses were performed using SAS9.1software.The correlation between categorical variables was estimated by Mann-Whitney U test.Spearman correlation coefficients were calculated to assess the correlations among continuous variables.Two-tailed Pvalues〈0.05 were considered as statistically significant.Results Comparing with healthy controls,the frequencies of TEMRAsubset in total CD8＋T cells were observed to decrease significantly（P=0.012）in CHB patients.In addition,PD-1expression on total CD8＋T cells and TEM subset was enhanced（P=0.018 and P=0.004,respectively）.Meanwhile,correlation analysis indicated that there was a positive correlation between the expression level of PD-1on CD8＋TEM and circulating HBV DNA（r=0.554,P=0.040）.Conclusions PD-1expression level on CD8＋TEM was increased significantly in CHB patients and correlated with the level of HBV DNA as well,indicating that HBV replication was probably associated with the activation of circulating CD8＋T cells,especially PD-1expression level on CD8＋TEMsubset.

关 键 词：肝炎 乙型 慢性 初始T细胞 中央记忆T细胞 效应记忆T细胞 终末效应记忆T细胞 PD-1 乙肝病毒DNA载量 

分 类 号：R512.62[医药卫生—内科学]