Intrahepatic levels of PD-1/PD-L correlate with liver inflammation in chronic hepatitis B.
OBJECTIVE
Programmed 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.
Chen
Ji
J
Department of Infectious Diseases, Peking University First Hospital, No 8, Xishiku Street, Xicheng District, Beijing 100034, People's Republic of China.
Wang
Xiao-Mei
XM
Wu
Xue-Jie
XJ
Wang
Yan
Y
Zhao
Hong
H
Shen
Bing
B
Wang
Gui-Qiang
GQ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D005260:Female; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006801:Humans; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D055815:Young Adult
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor