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

肝脏 ›› 2021, Vol. 26 ›› Issue (11): 1250-1252.

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

高得勇, 娄小丽, 马爽, 张昆仑, 刘亮明, 刘鸿翔

201699 上海市松江区中心医院感染科(高得勇,马爽,张昆仑,刘亮明),中心实验室(娄小丽),急诊危重病科(刘鸿翔)

收稿日期:2021-06-19 出版日期:2021-11-30 发布日期:2021-12-24
通讯作者: 高得勇,Email:gaodeyong1970@163.com; 刘鸿翔, Email: snakerjnyy@163.com
基金资助:
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)

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

GAO De-yong, LOU Xiao-li, MA Shuang, ZHANG Kun-lun, LIU Liang-ming, LIU Hong-xiang

1. Department of Infectious Diseases, Shanghai Songjiang Hospital, Shanghai 201699, China;
2. Department of Central laboratory, Shanghai Songjiang Hospital, Shanghai 201699, China;
3. Department of Emergency Critical Care Unit Shanghai Songjiang Hospital, Shanghai 201699, China

Received:2021-06-19 Online:2021-11-30 Published:2021-12-24
Contact: GAO De-yong, Email:gaodeyong1970@163.com; LIU Hong-xiang, Email: snakerjnyy@163.com

摘要/Abstract

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。

关键词: 乙型肝炎肝硬化, 抗病毒治疗, 抗原特异性CD8⁺T细胞

Abstract: 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.

Key words: Hepatitis B virus-related cirrhosis, Antiviral therapy, Function of antigen specific CD8⁺T cell

高得勇, 娄小丽, 马爽, 张昆仑, 刘亮明, 刘鸿翔. 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[J]. 肝脏, 2021, 26(11): 1250-1252.

GAO De-yong, LOU Xiao-li, MA Shuang, ZHANG Kun-lun, LIU Liang-ming, LIU Hong-xiang. Analysis on the function of antigen-specific CD8+ T cells before and after antiviral treatment in patients with hepatitis B virus-related cirrhosis[J]. Chinese Hepatolgy, 2021, 26(11): 1250-1252.

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