Abstract
Background and objective
Programed cell death-1 (PD-1) represents a mechanism of T-cell dysfunction in hepatitis B virus (HBV) persistence. In peripheral blood, PD-1 is up-regulated in virus-specific T cells, leading to the impairment of T cells. This study investigated the intrahepatic expression of PD-1 and its ligand (PD-L) in patients with chronic hepatitis B (CHB) virus.
Methods
Liver specimens were obtained from CHB (n = 56), acute hepatitis B (AHB, n = 12) patients and age-matched healthy subjects (n = 10). The expression of PD-1/PD-L was determined by immunohistochemistry.
Results
In CHB patients, PD-1 was predominantly expressed in lymphocytes infiltrating the portal tract. PD-L1 was detected in lymphocytes, hepatocytes and liver sinusoidal endothelial cells, while PD-L2 was localized in Kupffer cells and dendritic cells. The labeling indexes of PD-1 and PD-L1 in lymphocytes infiltrating portal area were significantly higher in CHB patients than in healthy controls and AHB patients. Within the CHB patients, the increases in labeling indexes of PD-1 and PD-L paralleled the degree of inflammation.
Conclusions
These results suggest that over-expression of PD-1, PD-L1 and PD-L2 within liver may participate in local immune dysfunction, which could be one of the mechanisms involved in the chronicity of HBV infection and chronic inflammation seen in CHB patients.
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Acknowledgments
We are most grateful to Professor Meng-dong Lan, Dr. Liang Zhang, Xiao-hong Shi and Professor Jing-Ming Zhao for help with technical support. This work was supported by the National Natural Science Foundation of China (No. 30771905), National Basic Research Program of China (“973” Program) (No. 2007CB512800), Mega-projects of Science Research (No. 008ZX10002-008) and Beijing Municipal Science & Technology Commission (No.D08050700650803).
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We have no conflict of interest in this study.
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Chen, J., Wang, XM., Wu, XJ. et al. Intrahepatic levels of PD-1/PD-L correlate with liver inflammation in chronic hepatitis B. Inflamm. Res. 60, 47–53 (2011). https://doi.org/10.1007/s00011-010-0233-1
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DOI: https://doi.org/10.1007/s00011-010-0233-1