title: Elevated frequency and function of regulatory T cells in patients with active chronic hepatitis C.
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+CD25(high) 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.
authors.affiliation: Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan.
authors.forename: Kuo-Chih
authors.initials: KC
authors.lastname: Tseng
authors.forename: Yun-Che
authors.initials: YC
authors.lastname: Ho
authors.forename: Yu-Hsi
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Ning-Sheng
authors.initials: NS
authors.lastname: Lai
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.forename: Chin
authors.initials: C
authors.lastname: Li
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000410:Alanine Transaminase