Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

, Volume 47, Issue 7, pp 823-833

First online:

Elevated frequency and function of regulatory T cells in patients with active chronic hepatitis C

  • Kuo-Chih TsengAffiliated withDepartment of Internal Medicine, Buddhist Dalin Tzu Chi General HospitalSchool of Medicine, Tzuchi University
  • , Yun-Che HoAffiliated withDepartment of Life Science, Institute of Molecular Biology, National Chung-Cheng University
  • , Yu-Hsi HsiehAffiliated withDepartment of Internal Medicine, Buddhist Dalin Tzu Chi General HospitalSchool of Medicine, Tzuchi University
  • , Ning-Sheng LaiAffiliated withDepartment of Internal Medicine, Buddhist Dalin Tzu Chi General HospitalSchool of Medicine, Tzuchi University
  • , Zhi-Hong WenAffiliated withDepartment of Marine Biotechnology and Resources, National Sun Yat-sen University
  • , Chin LiAffiliated withDepartment of Life Science, Institute of Molecular Biology, National Chung-Cheng University
  • , Shu-Fen WuAffiliated withDepartment of Life Science, Institute of Molecular Biology, National Chung-Cheng University Email author 

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Abstract

Background

Regulatory T cells (Tregs) play a pivotal role in the persistence of hepatitis C virus infection. The aim of this study was to evaluate the frequency and function of Tregs in patients with chronic hepatitis C (CHC).

Methods

We enrolled 44 CHC patients with elevated alanine aminotransferase (ALT) levels (CH group), 13 CHC patients with persistent normal ALT levels (PNALT group), and 14 age-matched healthy subjects (HS group; controls). Tregs were identified as CD4+, CD25+, and forkhead box P3 (Foxp3)+ T lymphocytes, using three-color fluorescence-activated cell sorting (FACS). The frequency of Tregs was determined by calculating the percentage of CD4+CD25high T cells among CD4 T cells. CD127 and CD45RA were also analyzed for subsets of Tregs. The levels of serum transforming growth factor (TGF)-β and interleukin (IL)-10 in immunosuppressive assays were detected by enzyme-linked immunosorbent assay (ELISA). The immunosuppressive abilities of Tregs were evaluated by measuring their ability to inhibit the proliferation of effector cells.

Results

Higher proportions of Tregs were found in the CH and PNALT groups compared with the HS group. The populations of CD127 low/negative and CD45RA negative cells were higher in the CH group than in the PNALT group. The expressions of IL-10 and TGF-β in the CH and PNALT groups were significantly higher than those in the HS group. In addition, the immunosuppressive ability of Tregs from the CH group was increased relative to that in the PNALT and the HS group.

Conclusions

CHC patients, irrespective of liver function, had higher frequencies of Tregs than healthy subjects; however, only CHC patients with inflammation showed enhanced immunosuppressive function of Tregs.

Keywords

Hepatitis C Immunosuppression Regulatory T cells