Title

Intrahepatic Levels of PD-1/PD-L Correlate with Liver Inflammation in Chronic Hepatitis B

Document Type

Article

Publication Date

1-2011

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.

DOI

10.1007/s00011-010-0233-1