title: [PD-1 expression in HBcAg-specific CD8+ T cells of adolescents with chronic HBV infection].
abstract: OBJECTIVE
  To investigate the differential expression of programmed death-1 (PD-1) in the hepatitis B core antigen (HBcAg)17-28-specific CD8+ T cell subsets of adolescent patients with chronic hepatitis B virus (HBV) infection during the immune tolerant phase and the immune clearance phase.
  
  
  METHODS
  A total of 105 patients between the ages of 12-28 years old (mean age 17.20+/-6.35) with chronic HBV infection and 15 healthy age-matched individuals were enrolled in the study. The patients were divided into two groups according to their current status in immune clearance phase (n = 55) or immune tolerant phase (n = 50), as determined by hepatic biopsy pathology. Flow cytometry was used to detect HLA-A2 type and PD-1 expression on peripheral blood mononuclear cells (PBMC) and HBcAg17-28-specific CD8+ T cells. PD-1 mRNA levels in PBMCs were measured by reverse transcription-polymerase chain reaction (RT-PCR). Independent samples t-test was used to compare means between the two groups, and one-way ANOVA was used to compare means among multiple groups. Pearson's correlation coefficient was used to assess the significance of correlation.
  
  
  RESULTS
  The frequency of HBcAg18-27-specific CD8+ T cells was significantly higher in the immune clearance phase group than in the immune tolerant phase group (t = 18.08, P less than 0.01), but the expression of PD-1 on the HBcAg18-27 specific CD8+ T cells was significantly lower in the immune clearance phase group than in the immune tolerant phase group (t = 4.72, P less than 0.01). A negative correlation existed between the frequency of HBcAg18-27-specific CD8+ T cells and PD-1 expression (r = -0.463, P less than 0.01). A positive correlation existed between HBV viral load and PD-1 expression on the HBcAg18-27-specific CD8+ T cells in chronic HBV infection patients (r = 0.882, P less than 0.01), and there was a negative correlation between PD-1 expression levels on HBcAg18-27-specific CD8+ T cells and hepatic tissue inflammation score (r = -0.76, P less than 0.01). PD-1 mRNA in PBMCs was significantly higher in the immune tolerant phase group than in the immune clearance phase group (t = 30.89, P less than 0.01).
  
  
  CONCLUSIONS
  Up-regulated expression of PD-1 is associated with HBV-specific CD8+ T cells and may play a crucial role in inhibiting their function during the immune tolerance phase of chronic HBV infection in adolescents.
authors.affiliation: Department of Infectious Diseases, the Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Zhou
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Zhou
authors.forename: Jun-Qing
authors.initials: JQ
authors.lastname: Li
mesh_terms: D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism
chemical_list: D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens