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通过核类同类抑制HBV减少PD-1表达在肝脏居民T细胞

Mireia García-López¹, Sabela Lens¹, Laura J Pallett²

¹Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain.

Liver international : official journal of the International Association for the Study of the Liver

|October 3, 2025

概括

在慢性乙型肝炎 (CHB) 患者中,T细胞上的肝内PD-1表达与病毒标志物相关. 核胺类同类 (NUC) 治疗降低PD-1,而停止治疗导致其重新表达.

科学领域:

免疫学免疫学免疫学
肝病学肝病学是一种肝病学.
病毒学病毒学

背景情况:

编程细胞死亡蛋白1 (PD-1) 表达肝脏T细胞是B型肝炎病毒 (HBV) 免疫疗法的目标.
慢性乙型肝炎 (CHB) 患者在肝脏内与循环淋巴细胞中表现出明显的PD-1表达模式.

研究的目的:

研究病毒抑制对肝脏内和循环淋巴细胞中的PD-1表达的影响.
探索肝脏内病毒标记物与肝脏T细胞上的PD-1表达之间的关系.

主要方法:

对22名CHB患者的血液和肝脏细针吸附剂 (FNA) 进行了分析,其中9名患者使用核胺类同类 (NUC).
肝脏内和血清病毒标记物被量化;流细胞计评估了淋巴细胞群.
来自独立的肝脏FNA队列的scRNAseq数据验证了这些发现.

主要成果:

在轻度肝炎中,PD-1表达在肝脏内CD8 T居住记忆细胞 (T_RM) 上与肝脏内HBVDNA (iHBV-DNA),ccccDNA和病毒转录标记 (cirB-RNA,HBcrAg) 相相关.
NUC治疗减少了CD8 T_RM上的PD-1表达,这种变化在循环T细胞中没有观察到.
停用NUC导致PD-1在CD8 T_RM上重新表达,而治疗开始则逆转了这种情况.

结论:

肝脏内病毒标记物与轻度肝炎的CHB患者肝脏T细胞上的PD-1表达有关.
长时间的NUC治疗会减少PD-1的表达,在停止治疗后重新表达,这表明有动态的免疫反应.

关键词:

在PD‐1中,抗病毒疗法是一种抗病毒疗法.卷积式封闭的圆形DNA.乙型肝炎病毒的感染.免疫反应的免疫反应.病毒生物标志物病毒生物标志物

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