J Gastroenterol DOI 10.1007/s00535-012-0544-9
ORIGINAL ARTICLE—LIVER, PANCREAS, AND BILIARY TRACT
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 •
Received: 20 June 2011 / Accepted: 11 January 2012 Ó Springer 2012
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 threecolor 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)-b 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-b 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 Á Immunosuppression Á 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
K.-C. Tseng Á Y.-H. Hsieh Á N.-S. Lai Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan K.-C. Tseng Á Y.-H. Hsieh Á N.-S. Lai School of Medicine, Tzuchi University, Hualien, Taiwan Y.-C. Ho Á C. Li Á S.-F. Wu (&) Department of Life Science, Institute of Molecular Biology, National Chung-Cheng University, No. 168, University Rd., Min-Hsiung, Chia-Yi 62102, Taiwan e-mail: firstname.lastname@example.org Z.-H. Wen Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan
Introduction Hepatitis C virus (HCV) is a small, enveloped, singlestranded, positive-sense RNA virus that belongs to the
family ﬂaviviridae and genus hepacivirus . After HCV infection, the immune systems of 55–85% of infected patients cannot eliminate the virus, and in these cases, chronic hepatitis C (CHC) may develop . Chronic hepatitis C is often asymptomatic, with persistently normal serum alanine aminotransferase (ALT) levels in 20–30% of patients, although it is usually associated with ﬂuctuating or persistently elevated ALT levels [2, 3]. Major long-term complications of CHC include cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC) . Retrospective and prospective studies on the long-term natural history of HCV infection have shown that 15–20% of CHC patients develop cirrhosis within 30 years . Once cirrhosis occurs, the annual risk of HCC, hepatic decompensation, and liver-related death is approximately 1–4, 5, and 2–4%, respectively [4–7]. After HCV...
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