title: Redistribution of regulatory T-cells across the evolving stages of chronic hepatitis C.
abstract: BACKGROUND
  Hepatitis C virus infection frequently leads to chronic hepatitis, possibly evolving to end-stage liver disease and hepatocellular carcinoma. Regulatory T cells can affect antiviral immune response thus influencing the outcome of the disease.
  
  
  OBJECTIVE
  To determine numeric and functional distribution of regulatory T cells expressing CD4+CD25hiFoxp3+ (T-regs) during the different stages of hepatitis C virus-related liver disease.
  
  
  METHODS
  90 hepatitis C viraemic patients and 50 healthy controls were included. Surface and intracellular (Foxp3) T-reg markers were evaluated by flow cytometry. Target cell proliferation and interferon-gamma production were evaluated in 37 HCV patients. In 16 cases intrahepatic distribution of Foxp3 by immuno-histochemistry was assessed.
  
  
  RESULTS
  T-regs were increased in hepatitis C virus infected patients and correlated inversely with aminotransferases and directly with MELD score and disease duration. A preserved inhibitory ability of interferon-gamma production was distinctive of patients with normal aminotransferases. Circulating T-regs did not correlate with intrahepatic distribution of Foxp3.
  
  
  CONCLUSIONS
  In chronic hepatitis C, selective expansion of peripheral T-regs in patients with normal aminotransferases and advanced disease suggests that, though a continual low level inflammation does not prevent liver disease progression, once cirrhosis has developed it may represent an attempt to prevent immuno-mediated decompensation.
authors.affiliation: Department of Clinical Medicine, University of Bologna, Bologna, Italy. silvia.ferri9@unibo.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferri
authors.forename: Claudine
authors.initials: C
authors.lastname: Lalanne
authors.forename: Giulia
authors.initials: G
authors.lastname: Lanzoni
authors.forename: Mirna
authors.initials: M
authors.lastname: Bassi
authors.forename: Sofia
authors.initials: S
authors.lastname: Asioli
authors.forename: Valentina
authors.initials: V
authors.lastname: Cipriano
authors.forename: Georgios
authors.initials: G
authors.lastname: Pappas
authors.forename: Paolo
authors.initials: P
authors.lastname: Muratori
authors.forename: Marco
authors.initials: M
authors.lastname: Lenzi
authors.forename: Luigi
authors.initials: L
authors.lastname: Muratori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D058625:End Stage Liver Disease / Q000097:blood / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood / Q000276:immunology; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase