Intrahepatic PD-1/PD-L1 Up-regulation Closely Correlates with Inflammation and Virus Replication in Patients with Chronic HBV Infection
Intrahepatic PD-1/PD-L1 Up-regulation Closely Correlates with Inflammation and Virus Replication in Patients with Chronic HBV Infection
复制标题
慢性 HBV 感染患者肝内 PD-1/PD-L1 上调与炎症和病毒复制密切相关
DOI：
10.1080/08820130903062210
复制
发表时间：
2009-01-01
影响因子：
2.8
通讯作者：
Wu, Yuzhang
中科院分区：
文献类型：
--
作者：
Xie, Zhunyi;Chen, Yongwen;Wu, Yuzhang
慢性乙型肝炎的特点是对受感染肝细胞的免疫反应波动，导致肝脏炎症和病毒持续存在。最近，程序性死亡-1（PD-1）及其配体PD-L1已被证明在平衡急性乙型肝炎患者肝脏的抗病毒免疫和炎症方面发挥着重要作用，显着影响疾病转归。外周T细胞中PD-1的上调与慢性乙型肝炎患者的免疫功能障碍有关。然而，PD-1/PD-L1对慢性HBV感染患者的肝损伤和慢性感染状态的影响仍不清楚。在这里，我们报告了 32 名慢性 HBV 患者的肝活检中 PD-1 和 PD-L1 的表达上调，与 4 名健康捐赠者相比。 PD-1/PD-L1 上调与肝脏炎症和 ALT 升高显着相关。此外，慢性乙型肝炎活动期PD-L1的适当上调但不过度表达以及肝脏驻留抗原呈递细胞（包括Kupffer细胞和肝窦内皮细胞）非活动期PD-L1的较低表达可能有助于病毒抑制。我们的数据表明，PD-1 和 PD-L1 的肝内相互作用可能在平衡慢性 HBV 感染中对 HBV 的免疫反应和免疫介导的肝损伤方面发挥重要作用。
Chronic hepatitis B was characterized by fluctuant immune response to infected hepatocytes resulting in hepatic inflammation and virus persistence. Recently, Programmed Death-1 (PD-1) and its ligand PD-L1 have been demonstrated to play an essential role in balancing antiviral immunity and inflammation in the livers of acute hepatitis B patients, significantly influencing disease outcome. PD-1 up-regulation in peripheral T cells is associated with immune dysfunction in chronic hepatitis B patients. However, the effect of PD-1/PD-L1 on hepatic damage and chronic infective status is still unknown in patients with chronic HBV infection. Here, we report up-regulation of PD-1 and PD-L1 in liver biopsies from 32 chronic HBV patients compared to 4 healthy donors. PD-1/PD-L1 up-regulation was significantly associated with hepatic inflammation and ALT elevation. Moreover, appropriate up-regulation but not overexpression of PD-L1 in the active phase of chronic hepatitis B as well as lower expression of PD-L1 in the inactive phase in liver residential antigen presenting cells (including Kupffer cells and sinusoidal endothelial cells) may contribute to viral inhibition. Our data suggest that the intrahepatic interaction of PD-1 and PD-L1 might play an important role in balancing the immune response to HBV and immune-mediated liver damage in chronic HBV infection.