Journal of Gastroenterology

, Volume 47, Issue 7, pp 823–833

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

  • Kuo-Chih Tseng
  • Yun-Che Ho
  • Yu-Hsi Hsieh
  • Ning-Sheng Lai
  • Zhi-Hong Wen
  • Chin Li
  • Shu-Fen Wu
Original Article—Liver, Pancreas, and Biliary Tract

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 

Abbreviations

HCV

Hepatitis C virus

CHC

Chronic hepatitis C

ALT

Alanine aminotransferase

HCC

Hepatocellular carcinoma

NK

Natural killer

Treg

Regulatory T cell

Foxp3

Forkhead box P3

TGF

Transforming growth factor

IL-10

Interleukin-10

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Copyright information

© Springer 2012

Authors and Affiliations

  • Kuo-Chih Tseng
    • 1
    • 2
  • Yun-Che Ho
    • 3
  • Yu-Hsi Hsieh
    • 1
    • 2
  • Ning-Sheng Lai
    • 1
    • 2
  • Zhi-Hong Wen
    • 4
  • Chin Li
    • 3
  • Shu-Fen Wu
    • 3
  1. 1.Department of Internal MedicineBuddhist Dalin Tzu Chi General HospitalChia-YiTaiwan
  2. 2.School of Medicine, Tzuchi UniversityHualienTaiwan
  3. 3.Department of Life ScienceInstitute of Molecular Biology, National Chung-Cheng UniversityChia-YiTaiwan
  4. 4.Department of Marine Biotechnology and ResourcesNational Sun Yat-sen UniversityKaohsiungTaiwan

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