title: Natural course of chronic hepatitis B is characterized by changing patterns of programmed death type-1 of CD8-positive T cells.
abstract: OBJECTIVE
  To investigate if and how programmed death type-1 (PD-1) expression affects the natural course of hepatitis B virus (HBV) infection.
  
  
  METHODS
  Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study. PD-1 expression in total T cells was detected by flow cytometry. Levels of total CD8+ T cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/PD-L1 blockage.
  
  
  RESULTS
  The PD-1 expression in T cells was dynamically changed during the natural course of chronic HBV infection, did not significantly increase in the immune tolerance phase, and returned to normal in the inactive virus carrier stage. Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection. However, it could significantly restore the T-cell response in the immune clearance stage of chronic HBV infection. Furthermore, the PD-1 expression level in T cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection.
  
  
  CONCLUSIONS
  The PD-l/PD-L1 pathway plays a different role in T-cell response during the natural course of chronic HBV infection.
authors.affiliation: Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Liang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Chen-Zhong
authors.initials: CZ
authors.lastname: Li
authors.forename: Mo-Bin
authors.initials: MB
authors.lastname: Wan
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D016923:Cell Death / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000410:Alanine Transaminase