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目的:观察替诺福韦酯(TDF)抗病毒治疗对HBeAg阳性慢性乙型肝炎患者外周血HBV特异性CD8n +T细胞功能的影响,评估其与HBeAg血清学阴转的相关性。n 方法:纳入2016年10月至2018年7月就诊的HLA-A02限制性HBeAg阳性慢性乙型肝炎患者63例,予以TDF(300 mg/d)抗病毒治疗,分选基线和治疗48周时外周血CD8n +T细胞,流式细胞术检测外周血T细胞计数,酶联免疫斑点试验检测分泌穿孔素、颗粒酶B和γ干扰素(IFN-γ)的HBV特异性CD8n +T细胞频数,建立HBV特异性CD8n +T细胞与HepG2.2.15细胞直接接触和间接接触共培养系统,检测培养上清液中HBV DNA,通过检测乳酸脱氢酶水平计算靶细胞死亡率,酶联免疫吸附试验检测细胞因子表达,评估病毒特异性CD8n +T细胞的细胞杀伤和非细胞杀伤功能。2组计量资料比较采用n t检验或配对n t检验。n 结果:TDF治疗48周时病毒学应答率为100%,生化学应答率为90.48%(57/63),HBeAg阴转率为25.40%(16/63)。外周血T细胞计数在TDF治疗48周时与基线及对照组比较差异均无统计学意义(n P > 0.05)。TDF治疗48周时,CHB患者分泌穿孔素、颗粒酶B和IFN-γ的HBV特异性CD8 n +T细胞频数较基线显著升高(n P 0.05). At 48 weeks of TDF treatment, the frequency of HBV-specific CD8 n +T cells secreting perforin, granzyme B, and IFN-γ in CHB patients was significantly higher than baseline (n P < 0.001). Furthermore, the frequency of HBV-specific CD8 n +T cells secreting perforin, granzyme B, and IFN-γ was also significantly higher in CHB patients with HBeAg negative than that of non-negative (n P < 0.05). HBV-specific CD8 n +T cells had induced significant down-regulation of HBV DNA in the supernatant of HepG2.2.15 cell culture (n P < 0.001) and remarkable IFN-γ and interleukin-2 secretion ( n P < 0.05) at 48 weeks of TDF therapy in direct and indirect contact co-culture system. However, HepG2.2.15 cells death rate induced by virus-specific CD8 n +T cells was increased only in the direct contact co-culture system (21.7% ± 6.18% vs. 16.1% ± 4.15%, n P < 0.001). Compared with HBeAg non-negative patients, HBeAg negative CHB patients with HBV-specific CD8 n +T cells had induced a strong decrease in HBV DNA (n P < 0.001) and an increase in IFN-γ secretion level ( n P 0.05).n Conclusion:During TDF treatment, with the viral load reduction, virus-specific CD8n +T cells cytokilling and non-cytokilling functions are significantly enhanced, and are closely related to HBeAg negative.n