Elevated Frequency and Function of Regulatory T Cells in Patients

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
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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

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