title: Pegylated interferon α enhances recovery of memory T cells in e antigen positive chronic hepatitis B patients.
abstract: BACKGROUND
  Interferons (IFNs) are a group of cytokines commonly used in the clinical treatment of chronic hepatitis B (CHB) patients. Their therapeutic effects are highly correlated with recovery of host antiviral immunity. Clearance of hepatitis B virus (HBV) is mediated partially by activated functional memory T cells. The aims of the present study were to investigate memory T cell status in patients with different outcomes following pegylated interferon-α (IFN-α) therapy and to identify new biomarkers for predicting antiviral immune responses.
  
  
  METHODS
  Peripheral blood cells were isolated from 23 CHB patients who were treated with pegylated IFN-α at week 0 (baseline) and week 24. Co-expression of programmed death-1 (PD-1) and CD244 in CD45RO positive T cells, as well as a subset of CD127 and CXCR4 positive memory T cells were assessed. In addition, perforin, granzyme B, and interferon-γ (IFN-γ) expressions were also analyzed by flow cytometric analysis after intracytoplasmic cytokine staining (ICCS). Peripheral blood mononuclear cells (PBMC) isolated at week 24 were re-challenged with exogenous HBV core antigen, and the percentage of IFN-γ expression, serum HBV DNA loads, and ALT (alanine aminotransferase) levels were evaluated.
  
  
  RESULTS
  At week 24, PD-1 and CD244 expression in CD8 memory T cells were down-regulated (P < 0.05, P < 0.05, respectively), along with decreased HBV DNA loads (P < 0.05), while the expressions of partial effector molecules in CD8 and CD4 memory T cells was up-regulated (P < 0.05,P < 0.05, respectively), especially in the responders. CD127 and CXCR4 were highly expressed in CD8 memory T cells after pegylated IFN-α treatment (P < 0.05), which was inversely correlated with HBV DNA loads (r = -0.47, P = 0.001). The responders had a higher IFN-γ expression in memory T cells than the non-responders did after HBV antigen re-stimulation in vitro.
  
  
  CONCLUSIONS
  Pegylated IFN-α treatment enhanced recovery of memory T cells in CHB patients by down-regulating inhibitory receptors and up-regulating effector molecules. The expressions of CXCR4 and CD127 in CD8 memory T cell may be used as biomarkers for predicting the outcome of treatment.
authors.affiliation: Department of Infectious Diseases and Research Center for Liver Diseases, Peking University First Hospital, Beijing, 100034, People's Republic of China.
authors.forename: Yong Zhe
authors.initials: YZ
authors.lastname: Liu
authors.forename: Feng Qin
authors.initials: FQ
authors.lastname: Hou
authors.forename: Peng
authors.initials: P
authors.lastname: Ding
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Ren
authors.forename: Shi Hong
authors.initials: SH
authors.lastname: Li
authors.forename: Gui Qiang
authors.initials: GQ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha