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Intrahepatic levels of PD-1/PD-L correlate with liver inflammation in chronic hepatitis B

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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).

Conflict of interest

We have no conflict of interest in this study.

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China

    Ji Chen, Xue-Jie Wu, Yan Wang, Hong Zhao & Gui-Qiang Wang

  2. Department of Pathology, Beijing Ditan Hospital, No. 8, Jingshun East Road, Chaoyang District, Beijing, 100015, People’s Republic of China

    Xiao-Mei Wang & Bing Shen

  3. Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing, 10034, People’s Republic of China

    Gui-Qiang Wang

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  1. Ji Chen
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  4. Yan Wang
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Correspondence to Gui-Qiang Wang.

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Responsible Editor: Kumar Visvanathan.

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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

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