title: Frequency of regulatory T-cell and hepatitis C viral antigen-specific immune response in recurrent hepatitis C after liver transplantation.
abstract: BACKGROUND
  Regulatory T (Treg) and type 1 regulatory T (Tr1) cells facilitate hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT). However, their frequencies and effects on HCV-specific immune responses have not been well investigated.
  
  
  METHODS
  We determined Treg and Tr1 frequencies in OLT patients with hepatitis C and assessed their associations with HCV-specific T cell responses. These patients comprised the following groups: an early post-transplantation group (n=14); an OLT-chronic active hepatitis C group (n=14) with active hepatitis C (alanine aminotransferase of>upper limit of normal/positive for HCV-RNA); an OLT-persistently normal alanine aminotransferase group (n=12) without active hepatitis C (not interferon/positive for HCV-RNA); and an OLT-sustained viral response group (n=6) with sustained viral responses using interferon treatment (negative for HCV-RNA). The frequencies of HCV-specific CD4+ T cells that secreted interferon-γ were determined by enzyme-linked immunosorbent spot assay (except for the OLT early group).
  
  
  RESULTS
  Treg and Tr1 frequencies were low during the early post-transplantation period. OLT patients with sustained viral responses had lower Treg frequencies than those with chronic hepatitis C, whereas Tr1 frequencies were significantly reduced in OLT patients with persistently normal alanine aminotransferase levels compared to those with chronic hepatitis C (p<0.05). Treg frequencies positively correlated with HCV NS3 antigen-specific interferon-γ responses, which corresponded to HCV clearance.
  
  
  CONCLUSIONS
  Increased Treg frequencies and reduced HCV-NS3 antigen-specific responses recovered after viral eradication in post-OLT chronic hepatitis C patients. Reduced Tr1 frequencies were associated with hepatitis activity control, which may facilitate controlling chronic hepatitis C in patients after OLT.
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Utsumi
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address: akitaka@md.okayama-u.ac.jp.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Umeda
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Koike
authors.affiliation: Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Napier
authors.affiliation: Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sadamori
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Shinoura
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nobuoka
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.affiliation: Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki 701-0193, Okayama, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Yagi
mesh_terms: D000368:Aged; D005260:Female; D005434:Flow Cytometry; D006526:Hepatitis C / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D018936:Hepatitis C Antigens
keywords: Chronic hepatitis C; Living donor liver transplantation; Persistently normal alanine aminotransferase; Regulatory T cell; Sustained viral response; Type 1 regulatory T cells