title: Intrahepatic levels of PD-1/PD-L correlate with liver inflammation in chronic hepatitis B.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Peking University First Hospital, No 8, Xishiku Street, Xicheng District, Beijing 100034, People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Wang
authors.forename: Xue-Jie
authors.initials: XJ
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.forename: Gui-Qiang
authors.initials: GQ
authors.lastname: Wang
mesh_terms: 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
chemical_list: 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