乙型肝炎肝硬化抗病毒治疗前后抗原特异性CD8^(+)T细胞功能分析  

Analysis on the function of antigen-specific CD8^(+)T cells before and after antiviral treatment in patients with hepatitis B virus-related cirrhosis

作　　者：高得勇 娄小丽 马爽[1] 张昆仑 刘亮明[1] 刘鸿翔[3] GAO De-yong;LOU Xiao-li;MA Shuang;ZHANG Kun-lun;LIU Liang-ming;LIU Hong-xiang(Department of Infectious Diseases,Shanghai Songjiang Hospital,Shanghai 201699,China;Department of Central laboratory,Shanghai Songjiang Hospital,Shanghai 201699,China;Department of Emergency Critical Care Unit Shanghai Songjiang Hospital,Shanghai 201699,China)

机构地区：[1]上海市松江区中心医院感染科,201699 [2]上海市松江区中心医院中心实验室,201699 [3]上海市松江区中心医院急诊危重病科,201699

出　　处：《肝脏》2021年第11期1250-1252,1256,共4页Chinese Hepatology

基　　金：上海市卫生和计划生育委员会面上项目(201740211);上海市松江区科技攻关项目(20SJKJGG9);上海市松江区卫生和计划生育委员会重点项目(2012-Ⅲ-06)。

摘　　要：目的观察乙型肝炎肝硬化抗病毒治疗前后外周血HBV抗原特异性T细胞的数量功能与临床预后的相关性。方法经HLA-A2分型检测选取46例患者,采用主要组织相容性复合物(MHC)-抗原肽四聚体标记技术,经流式细胞仪检测乙型肝炎肝硬化患者抗病毒治疗前后外周血HBV抗原特异性CD8^(+)T细胞百分比,并对其细胞因子分泌能力及表型进行检测分析。结果46例人类白细胞相关抗原HLA-A2阳性者中,检出抗原特异性CD8^(+)T细胞表达的为22例。TDF治疗后患者ALT为(31.29±18.42)U/L,较治疗前(124.05±29.18)U/L明显下降(t=72,P=0.015),HBV DNA全部转阴,转阴率为100%。治疗后抗原特异性的CD8^(+)T细胞数量为(1.15±0.37)%,明显高于治疗前的(0.65±0.25)%(t=59,P<0.01);治疗后γ干扰素为(6.86±2.08)%,明显高于治疗前(3.58±1.26)%(t=46,P<0.01);抗病毒治疗后HBV表位特异性的CD8^(+)T细胞表达抑制性因子PD-1的细胞百分比为(0.43±0.19)%,低于治疗前的(0.76±0.43)%(t=131,P=0.0084);HBV表位特异性的CD8^(+)T细胞表达活性因子CD28的细胞百分比为(1.03±0.45)%,高于治疗前的(0.56±0.26)%(t=100,P=0.0006)。结论乙型肝炎肝硬化患者外周血中抗原特异性CD8^(+)T细胞存在功能缺陷,经抗病毒治疗后抗原特异性CD8^(+)T细胞数量和功能有一定程度的增强。Objective To investigate the number and function of hepatitis B virus(HBV)antigen-specific T cells in peripheral blood before and after antiviral treatment of HBV-related cirrhosis,and its correlation with clinical prognosis.Methods Forty-six patients were selected by HLA-A2 classification test,the percentages of HBV antigen-specific T cells in the peripheral blood were detected before and after treatment by flow cytometry through the major histocompatibility complex(MHC)-antigenic peptide tetramer staining,the cytokines secreting ability and phenotype of the cells were detected.Results Human leukocyte-associated antigens HLA-A2 expressed by antigen-specific CD8^(+)T cells were detected in 22 patients,the level of liver function marker alanine aminotransferase(ALT)after treatment(31.29±18.42)was significantly lower than that before treatment(124.05±29.18),(u=72,P=0.015),and the HBV DNA negative rate was 100%.The number of antigen-specific CD8^(+)T cells after treatment(1.15±0.37)%was significantly higher than that before treatment(0.65±0.25)%,(u=59,P<0.0001).The percentage of cells which secreted interferon(IFN-γ)after treatment(6.86±2.08)%was significantly higher than that before treatment(3.58±1.26)%,(u=46,P<0.0001).The percentage of HBV epitope-specific CD8^(+)T cells which expressed inhibitory factor PD-1 after treatment(0.43±0.19)%was significantly lower than that before treatment(0.76±0.43)%,(u=131,P<0.05).The percentage of HBV epitope-specific CD8^(+)T cells which expressed active factor CD28 after treatment(1.03±0.45)%was significantly higher than that before treatment(0.56±0.26)%,(u=100,P=0.0006).Conclusion The function of antigen-specific CD8^(+)T cells in the peripheral blood of patients with HBV-related cirrhosis is defected.After antiviral treatment,the number and function of antigen specific CD8^(+)T cells are both improved.

关 键 词：乙型肝炎肝硬化 抗病毒治疗 抗原特异性CD8^(+)T细胞 

分 类 号：R512.62[医药卫生—内科学] R575.2[医药卫生—临床医学]