title: Programmed death-1 expression is associated with the disease status in hepatitis B virus infection.
abstract: OBJECTIVE
  To define the potential role of programmed death-1/programmed death-ligand (PD-1/PD-L) pathway in different hepatitis B virus (HBV) infection disease status; we examined the expression of PD-1 on antigen specific CD8+ T cells in peripheral blood of patients with chronic hepatitis B (CHB) and acute exacerbation of hepatitis B (AEHB) infection.
  
  
  METHODS
  The PD-1 level on CD8+ T lymphocytes and the number of HBV specific CD8+ T lymphocytes in patients and healthy controls (HCs) were analyzed by staining with pentameric peptide-human leukocyte antigen2 (HLA2) complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction (PCR) was used to measure the serum HBV-DNA levels.
  
  
  RESULTS
  The level of PD-1 expression on total CD8+ T cells in CHB patients (13.86% +/- 3.38%) was significantly higher than that in AEHB patients (6.80% +/- 2.19%, P < 0.01) and healthy individuals (4.63% +/- 1.23%, P < 0.01). Compared to AEHB patients (0.81% +/- 0.73%), lower frequency of HBV-specific CD8+ T cells was detected in chronic hepatitis B patients (0.37% +/- 0.43%, P < 0.05). There was an inverse correlation between the strength of HBV-specific CD8+ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8+ T cells in CHB and AEHB subjects (R = 0.541, P < 0.01). However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase (ALT) levels (R = 0.066, P > 0.05).
  
  
  CONCLUSIONS
  Our results confirm previous reports that HBV specific CD8+ T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B with persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8+ T cell response.
authors.affiliation: Department of Hepatology and Infectious Disease,Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Pian
authors.initials: P
authors.lastname: Ye
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Weng
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Zhang
authors.forename: Jian-Ao
authors.initials: JA
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Dong
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Jie
authors.forename: Ran
authors.initials: R
authors.lastname: Pang
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Wei
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D015703:Antigens, CD / Q000097:blood* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood; D006509:Hepatitis B / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000473:pathology*; D006801:Humans; D061026:Programmed Cell Death 1 Receptor; D012720:Severity of Illness Index; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000410:Alanine Transaminase