1. Longitudinal fluctuations in PD1 and PD-L1 expression in association with changes in anti-viral immune response in chronic hepatitis B
- Author
-
Shaikh Abdul Lateef, Zhang Wenjin, Wan Yunle, Peng Chuanhui, and Zheng Shusen
- Subjects
Adult ,Male ,PD-L1 ,HBsAg ,medicine.medical_specialty ,Hepatitis B virus ,Biopsy ,T-Lymphocytes ,Programmed Cell Death 1 Receptor ,Inflammation ,medicine.disease_cause ,B7-H1 Antigen ,Immune system ,Hepatitis B, Chronic ,Internal medicine ,HLA-A2 Antigen ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,lcsh:RC799-869 ,Hepatitis B Surface Antigens ,medicine.diagnostic_test ,biology ,business.industry ,Gastroenterology ,Alanine Transaminase ,General Medicine ,Hepatitis B ,Hepatology ,medicine.disease ,Flow Cytometry ,Immunohistochemistry ,digestive system diseases ,PD1 ,Alanine transaminase ,Liver ,Liver biopsy ,Immunology ,DNA, Viral ,biology.protein ,Cytokines ,Female ,lcsh:Diseases of the digestive system. Gastroenterology ,medicine.symptom ,business ,Research Article - Abstract
Background Controversy 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. Methods Fifteen 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. Conclusion The 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.
- Published
- 2012