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Intrahepatic status of regulatory T cells in autoimmune liver diseases and chronic viral hepatitis.
Authors:Masashi Sakaki  Kazumasa Hiroishi  Toshiyuki Baba  Takayoshi Ito  Yuichi Hirayama  Koji Saito  Takahiko Tonoike  Miki Kushima  Michio Imawari
Institution:Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Abstract:Aim: 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). Conclusion: 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.
Keywords:autoimmune hepatitis  chronic hepatitis  forkhead box P3  primary biliary cirrhosis  regulatory T cells
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