title: Induction of regulatory T-cells and interleukin-10-producing cells in non-responders to pegylated interferon-alpha therapy for chronic hepatitis B.
abstract: BACKGROUND
  Treatment with interferon-alpha (IFN-alpha) leads to a response in only a minority of patients with chronic hepatitis B virus (HBV) infection, but the reasons for this are poorly understood. It was recently shown that in patients with chronic HBV infection, CD4+CD25+ regulatory T-cells (Treg) can suppress the HBV-specific immune response. We aimed to investigate whether in non-responders to IFN-alpha therapy Treg contribute to treatment failure by downregulating the HBV-specific T-cell responses.
  
  
  METHODS
  Fourteen patients positive for hepatitis B e antigen received pegylated IFN-alpha monotherapy for 52 weeks and were followed for 26 weeks.
  
  
  RESULTS
  Compared with non-responders, responders displayed an increased HBV-specific T-helper cell proliferation. At the start of treatment there was no difference in the frequencies of CD4+CD25+ Treg between responders and non-responders. During therapy, the frequency of CD4+CD25+ Treg increased in non-responders, but not in responders. In contrast to the responders, the non-responders showed a significant increase in the frequency of interleukin-10-producing cells. Treg depletion resulted in increased proliferation capacity, but did not affect the frequency of interleukin-10-producing cells measured during the course of the treatment.
  
  
  CONCLUSIONS
  This study indicates that Treg might have an important role in HBV persistence during and after pegylated IFN-alpha therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Dave
authors.initials: D
authors.lastname: Sprengers
authors.forename: Jeroen N
authors.initials: JN
authors.lastname: Stoop
authors.forename: Rekha S
authors.initials: RS
authors.lastname: Binda
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.forename: Bart L
authors.initials: BL
authors.lastname: Haagmans
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carotenuto
authors.forename: Andre
authors.initials: A
authors.lastname: Artsen
authors.forename: Renate G
authors.initials: RG
authors.lastname: van der Molen
authors.forename: Harry L
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016753:Interleukin-10; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b