慢性 HCV 感染病毒清除后体外 T 细胞功能的动态变化。
Dynamic Changes in Ex Vivo T-Cell Function After Viral Clearance in Chronic HCV Infection.
机构信息
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
The Catholic University Liver Research Center, Department of Internal Medicine, College of Medicine, Daejeon, Republic of Korea.
出版信息
J Infect Dis. 2019 Sep 13;220(8):1290-1301. doi: 10.1093/infdis/jiz291.
BACKGROUND
Direct-acting antiviral (DAA) agents can successfully treat chronic hepatitis C virus (HCV) infection. However, the ex vivo HCV-specific T-cell function following viral clearance remains unknown.
METHODS
We investigated functional alterations and phenotypic changes in ex vivo HCV-specific CD8+ T cells with a longitudinal analysis of 41 patients with chronic HCV infection who were undergoing DAA treatment.
RESULTS
A patient subset exhibited a significantly increased T-cell response (mainly CD8+ T cells) at week 4 of treatment. However, this increased T-cell response diminished in later weeks. Relative to pretreatment levels, the ex vivo HCV-specific CD8+ T-cell frequency decreased at 12 weeks after the end of treatment, along with a decreased antigen-experienced CD8+ T-cell population. DAA treatment increased the proliferative capacity of HCV-specific CD8+ T cells, but this change was not correlated with ex vivo function. Patients experiencing viral breakthrough or relapse exhibited defective restoration of T-cell function.
CONCLUSION
Our present results indicated that DAA-mediated viral clearance only transiently restored ex vivo T-cell function, suggesting a need to enhance T-cell function in DAA-treated patients.
背景
直接作用抗病毒（DAA）药物可成功治疗慢性丙型肝炎病毒（HCV）感染。然而，清除病毒后 HCV 特异性 T 细胞的体外功能仍不清楚。
方法
我们对 41 例接受 DAA 治疗的慢性 HCV 感染患者进行了纵向分析，研究了 HCV 特异性 CD8+T 细胞的功能改变和表型变化。
结果
治疗第 4 周，患者亚组出现明显的 T 细胞反应（主要为 CD8+T 细胞）增加。然而，这种增加的 T 细胞反应在随后的几周内减弱。与治疗前水平相比，治疗结束后 12 周时，体外 HCV 特异性 CD8+T 细胞频率下降，同时抗原经验丰富的 CD8+T 细胞群体减少。DAA 治疗增加了 HCV 特异性 CD8+T 细胞的增殖能力，但这种变化与体外功能无关。发生病毒突破或复发的患者表现出 T 细胞功能恢复缺陷。
结论
我们的研究结果表明，DAA 介导的病毒清除仅短暂地恢复了体外 T 细胞功能，这表明需要增强 DAA 治疗患者的 T 细胞功能。
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