title: Intrahepatic status of regulatory T cells in autoimmune liver diseases and chronic viral hepatitis.
abstract: OBJECTIVE
  Regulatory T cells (Tregs) maintain immunological tolerance and suppress autoreactive immune responses. We evaluated the intrahepatic status of Tregs in patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), chronic hepatitis C (CH-C), or chronic hepatitis B (CH-B).
  
  
  METHODS
  We analyzed 85 patients (20 AIH, 22 PBC, 27 CH-C, and 16 CH-B) and 14 controls. Using liver tissue samples obtained by needle biopsy or from marginal parts of resected metastatic liver tumors in the controls, immunohistochemical analyses of forkhead box P3(+), which is a specific marker for Tregs, CD4(+), and CD8(+) cells were performed.
  
  
  RESULTS
  Intrahepatic Tregs were significantly more infiltrated in patients with liver diseases than in the controls. There were significantly fewer intrahepatic Tregs in the AIH patients than in the PBC patients (P = 0.037). Patients with alow frequency of intrahepatic Tregs were detected significantly more in the AIH and CH-B groups than in the PBC and CH-C groups (P < 0.05). In addition, the frequency of Tregs decreased in the liver of PBC patients as the pathological stage of the disease advanced. We found significantly less infiltration of CD4(+) T cells in AIH than in other diseases (P < 0.05). Liver-infiltrating CD8(+) T cells were detected more frequently in the CH-B group than in other groups (P < 0.003).
  
  
  CONCLUSIONS
  Intrahepatic Tregs were increased in both patients with autoimmune liver diseases and those with viral hepatitis. In autoimmune liver diseases, intrahepatic Tregs were fewer in the AIH patients than in the PBC patients.
authors.affiliation: Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sakaki
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hiroishi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Baba
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ito
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirayama
authors.forename: Koji
authors.initials: K
authors.lastname: Saito
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tonoike
authors.forename: Miki
authors.initials: M
authors.lastname: Kushima
authors.forename: Michio
authors.initials: M
authors.lastname: Imawari