慢性HBV感染状态下PD1_PD-L1的表达研究.docVIP

 慢性 HBV 感染状态下 PD1/PD-L1 的表达 研究# 张文瑾* 5 10 15 20 25 30 （浙江大学医学院附属第一医院，杭州 310031） 摘要：关于免疫抑制受体 PD1 和 PD-L1 在 HBV 感染慢性化的机制研究，长期以来存在争论。 有观点认为 PD1 和 PD-L1 的高表达抑制了淋巴细胞的增值和细胞毒作用，从而导致了抗原特 异性免疫应答的水平下降，由此导致 HBV 持续感染。另有观点认为 PD1 和 PD-L1 的高表达是 机体维持稳态的需要，避免过度的免疫炎症反应造成的严重组织损伤。本研究以慢性肝炎活 动状态的患者为研究对象，根据转氨酶和肝组织 CD8+淋巴细胞的浸润数将炎症时段分为 1 至 4 期，期中于炎症高峰期，PD1 和 PD-L1 的表达水平最高；随着炎症程度的降低，期表达 水平也随之下降。而且正负协同刺激分子在细胞水平均呈共表达状态。根据本实验结果，我 们认为在免疫炎症反应过程中，正负协同刺激分子的表达处于平衡状态，免疫抑制受体的高 表达是限制炎症反应程度的需要，而非特异性地抑制 HBV 特异性免疫应答。 关键词：免疫耐受；HBV；B7H1 中图分类号：R392 The study of PD1/PD-L1 expression in chronic hepatitis B patients Zhang Wenjin (First Affiliated Hospital, School of Medicine, Zhejiang University, HangZhou 310031) Abstract: There is controversy about the role of PD1 and PD-L1 in persistent HBV infection. In some studies, HBV persistent infection was attributed to high level of PD-1 and PD-L1 expression on HBV specific T cells and antigen presenting cells (APC) respectively. Other studies revealed that the up-regulation of PD-1 and PD-L1 during acute inflammation phase is needed to maintain homeostasis by offset increasing positive co-stimulatory molecule signals to avoid severe pathology damage by over-vigorous immune response. In this study, the expression of PD-1 and PD-L1 in chronic hepatitis B patients was analyzed. Our results showed that the expression of PD-1/PD-L1 was up-regulated significantly in inflammation flare up period and was decreased when inflammation reduced. PD-1 and PD-L1 were co-expressed with their positive costimulatory partner. Based on our results, we got the conclusion that the up-regulation of negative costimulatory molecules were needed during inflammation period to maintain homeostasis by the balance of positive- costimulatory signals. Keywords: immune tolerance; HBV; B7H1 35 0 引言 近年来，有研究认为，乙肝病毒感染的慢性化是负向协同刺激分子表达上调的结果。其 中，抑制性 B7 家族分子：PD1，PD-L1，PD-L2 在乙肝病毒（HBV）持续感染状态下的高 水平表达，从而抑制抗原特异性 T 淋巴细胞功能（细胞增殖、细胞毒、细胞因子分泌）被 40 认为是 HBV 感染慢性化的机制之一[1,2,3,4]。PD 一 1 属于免疫球蛋白超家族成员，含有两个 酪氨酸信号基序的胞