慢性乙型肝炎病毒感染者不同疾病时期及Peg⁃干扰素抗病毒治疗前后T细胞及其亚群CD107a的变化  

Role of CD107a produced by T cells and their subsets in liver injury and antiviral therapy with Peg⁃inter⁃feron in chronic HBV infection

作　　者：顾琳[1] 黄泽旋 李静[1] 黄月华[1,2] 顾玉荣[2] GU Lin;HUANG Zexuan;LI Jing;HUANG Yuehua;GU Yurong(Guang-dong Provincial Key Laboratory of Liver Diseases,Guangzhou 510630,China;不详)

机构地区：[1]中山大学附属第三医院广东省肝脏病研究重点实验室,广州510630 [2]中山大学附属第三医院感染性疾病科,广州510630

出　　处：《实用医学杂志》2021年第24期3143-3147,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金(编号:81872006);国家重大专项(编号:2018ZX10732-101-002-004);广州市科技计划项目(编号:202002030431)。

摘　　要：目的观察慢性乙型肝炎病毒(HBV)感染者不同疾病时期及长效干扰素治疗前后外周血T细胞及其亚群CD107a分泌的细胞毒功能变化。方法将慢性HBV感染患者分为未抗病毒治疗组(n=300)和干扰素治疗组(n=36),再进一步将未抗病毒治疗组患者分成免疫耐受期(IT)组(n=29)、免疫活动期(IA)组(n=174)、非活动期(IC)组(n=44)和灰色区(GZ)组(n=53)。纳入17例健康志愿者作为健康对照(HC)组。采集外周血、利用流式细胞术检测T细胞CD107a,并进行统计分析。结果(1)免疫活跃期患者T细胞及其亚群(CD4及CD8 T细胞)CD107a分泌水平显著高于免疫耐受期及非活动期患者。(2)患者T细胞及其亚群CD107a分泌水平与肝脏炎症指标及纤维化指标均呈正相关。(3)与HBeAg(⁃)患者相比,HBeAg(+)患者T细胞及其亚群CD107a分泌水平更高,HBV DNA>10^(6) IU/mL患者也显著高于HBV DNA<10^(6) IU/mL患者。(4)与Peg干扰素抗病毒治疗前相比,治疗48周后,患者的T细胞及其亚群CD107a分泌能力显著提高(均P<0.0001)。结论慢性HBV感染者T细胞CD107a分泌的细胞毒作用与疾病状态及分期有关,且长效干扰素治疗可进一步增强T细胞的细胞毒作用。Objective To observe the changes of CD107a production by T cells and their subsets in peripheral blood at different stages of patients with chronic HBV infection and during the antiviral treatment with Peg⁃interferon,and to explore the rule of the change of T cell cytotoxicity during different stages of chronic HBV infection and antiviral therapy with interferon.Methods Patients with chronic HBV infection were enrolled into the study,with a cross⁃section cohort(n=300,treatment⁃naive)and a longitudinal cohort(n=36,HBeAg⁃positive,ALT>2 ULN,receiving Peg⁃interferon therapy after enrollment).Peripheral blood before and after antiviral treat⁃ment was collected from the two cohorts of patients.The production of CD107a by T cells was detected by flow cytometry.Results(1)The levels of CD107a produced by CD3^(+),CD4^(+) and CD8^(+)T cells in patients of immune⁃active stage(IA)were significantly higher than that in patients of immune⁃tolerant stage(IT)and inactive carrier stage(IC).(2)The levels of CD107a production by CD3^(+),CD4^(+) and CD8^(+)T cells was found positively correlated with liver inflammatory indexes(ALT,AST and total bilirubin).(3)The levels of CD107a production by CD3^(+),CD4^(+) and CD8^(+)T cells were also showed a significant positive correlation with liver fibrosis(liver stiffness measure⁃ment,APRI and FIB⁃4 score).(4)The levels of CD107a production by CD3^(+),CD4^(+) and CD8^(+)T cells were signifi⁃cantly higher in HBeAg(+)patients than those in HBeAg(-)patients,and those in patients with HBV DNA>10^(6) IU/mL was significantly higher than those in patients with HBV DNA<10^(6) IU/mL.(5)The levels of CD107a production by CD3^(+),CD4^(+) and CD8^(+)T cells were significantly increased after 48 weeks of treatment with PEG⁃interferon compared with those before treatment.Conclusion The cytotoxic effect of T cells to secret CD107a is not only positively correlated with liver inflammation and fibrosis,but also with HBV replication level.The cytotoxic effect of T cells is obvious highe

关 键 词：T淋巴细胞 CD107a 干扰素 HBV 

分 类 号：R512.62[医药卫生—内科学]