Longitudinal fluctuations in PD1 and PD-L1 expression in association with changes in anti-viral immune response in chronic hepatitis B

BMC Gastroenterology

Research Article

Wan Yunle¹  Peng Chuanhui²  Shaikh Abdul Lateef²  Zhang Wenjin²  Zheng Shusen² 

[1] Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510120, Guangzhou, Guangdong Province, China;Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, China;

关键词: PD1;    PD-L1;    Hepatitis B;   

DOI  :  10.1186/1471-230X-12-109

 received in 2012-03-11, accepted in 2012-08-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundControversy exists regarding the role of PD1 and its ligand PD-L1 in chronic hepatitis B infection. In some studies, persistent HBV infection has been attributed to high levels of PD-1 and PD-L1 expression on HBV-specific T-cells and antigen-presenting cells (APCs) respectively. Other studies revealed that the up-regulation of PD-1 and PD-L1 during an acute inflammation phase is required to offset increasing positive co-stimulatory signals to avoid severe damage by an over-vigorous immune response.MethodsFifteen chronic hepatitis B patients, with inflammatory flare episode, were recruited prospectively. Based on serum HBV-DNA, HBsAg load, and ALT values, inflammatory flare episode were divided into initial, climax, decline and regression phase. Blood sample and liver biopsy tissues from each individual were taken in these 4 phases respectively. Circulating and intra-hepatic PD1 and PD-L1 expression levels were monitored throughout the inflammatory flare episode by flow cytometry and immunostaining and these expression levels were related to the HBV-specific T-cell changes, expression of pro-inflammatory cytokines, HBV-DNA replication and HBV antigen load.Results]The levels of PD-1 and PD-L1 expressions were significantly up-regulated in the inflammation ascending phase, initial and climax period and in parallel with HBV-specific colon expansion. It showed increasing the level of serum ALT and decreasing the HBV-DNA loads. As the level of inflammation reduced, the circulating and intra-hepatic PD1 and circulating PD-L1 decreased progressively in concordance with serum ALT, HBV-DNA and HBsAg loads decreased except intra-hepatic PD-1 expression. Intra-hepatic PD-L1 expression did not decrease significantly during the regression phase of inflammation compared to that in prior period. The intra-hepatic PD-L1 expression remained relatively on higher level when serum HBV-DNA load and ALT decreased to approximately normal range.ConclusionThe relatively high level of intra-hepatic PD-L1 expression during the inflammatory regression period may contribute to constitute an immunosuppressive microenvironment, which facilitate persistent HBV infection via the inhibition of HBV-specific T cell clonal expansion.

【 授权许可】

Unknown   
© Wenjin et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.