title: [Hepatitis B e antigen from chronic hepatitis B patients induces Th1/Th2 cytokine imbalance in vitro].
abstract: OBJECTIVE
  To study the immunoregulatory effect of hepatitis B virus (HBV) e antigen (HBeAg) on peripheral blood monocytes (PBMCs).
  
  
  METHODS
  PBMCs were isolated from patients with chronic hepatitis B (CHB; both HBeAg- and HBeAg+) and healthy controls, and cultured with recombinant HBeAg. The HBeAg-induced changes in expression of PD-1/PD-L1 were measured by flow cytometry of the cells and in secreted cytokines were measured by enzyme-linked immunosorbent assay of the supernatants. Comparisons between two groups were made by the independent-samples t-test; the relationship between PD-1/B7-H1 level and HBV DNA copy number was evaluated by Spearman's correlation analysis.
  
  
  RESULTS
  Exposure to HBeAg led to a significant decrease in CD3+CD4+ T lymphocyte-specific expression of IFNa for both the CHB patients' and healthy controls' samples (t = 2.382 and -4.190 respectively, P less than 0.01). For the HBeAg- CHB patients' and healthy controls' samples, the HBeAg exposure led to increased levels of secreted cytokines IL-6, IL-10 and TNFa (t = 2.504, 3.583 and 4.324, P less than 0.01 and t = 3.542, 6.246 and 5.273, P less than 0.01 respectively) and of CD14+ PBMC-specific expression of PD-L1 (t = 4.815 and 3.454, P less than 0.05 respectively). Compared to the HBeAg-negative CHB patients' and healthy controls' samples, the HBeAg+ CHB patients' samples had significantly lower CD3+CD4+ T cell-specific expression of IFNa (t = -3.177 and -4.541, P less than 0.01 respectively), but significantly higher levels of secreted IL-4 (t = 3.382 and 4.393, P less than 0.01 respectively), of CD3+ T cells-specific expression of PD-1/PD-L1 (t = 4.755, 2.942 and 4.518, 4.595, P less than 0.01 respectively), and of CD14+ T cells-specific expression of PD-L1 (t = 5.092 and 5.473, P less than 0.01 respectively). The CD3+ T cells-specific expression of PD-L1 was significantly higher in the samples from HBeAg- CHB patients than from the healthy controls (t = 3.214, P less than 0.01).
  
  
  CONCLUSIONS
  HBeAg was able to down-regulate the production of Th1-type cytokines (IFNgamma), and up-regulate the secretion of Th2-type cytokines (IL-6, IL-10) and the expression of PD-1/PD-L1on monocytes. These changes are conducive to the formation of immune tolerance to HBV. Therefore, HBeAg may play an important role in immune tolerance to chronic HBV infection.
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ya-ping
authors.initials: YP
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Long-feng
authors.initials: LF
authors.lastname: Jiang
authors.forename: Qing-qing
authors.initials: QQ
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.forename: Nian
authors.initials: N
authors.lastname: Chen
authors.forename: Lian-hua
authors.initials: LH
authors.lastname: Kong
authors.forename: Fa-ren
authors.initials: FR
authors.lastname: Xie
authors.forename: Zu-hu
authors.initials: ZH
authors.lastname: Huang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology
chemical_list: D006513:Hepatitis B e Antigens; C573415:IFNG protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma