title: Naturally-occurring regulatory T cells are increased in inflamed portal tracts with cholangiopathy in primary biliary cirrhosis.
abstract: BACKGROUND
  Primary biliary cirrhosis (PBC) is an autoimmune liver disease targeting the intrahepatic small bile ducts showing chronic non-suppurative destructive cholangitis (CNSDC). Recent studies suggest that naturally-occurring CD4+CD25high regulatory T cells (Tregs) expressing Forkhead box P3 (Foxp3) play an active role in immunological self-tolerance.
  
  
  OBJECTIVE
  To investigate whether Foxp3+Tregs are involved in the pathogenesis of PBC.
  
  
  METHODS
  Foxp3+Tregs was detected immunohistochemically in livers from patients with PBC (n = 27), chronic viral hepatitis (CVH) (n = 15), and normal subjects (n = 10). The distribution of Tregs in portal tracts was semi-quantitatively evaluated in each groups. Levels of Foxp3, IL-10, TGFbeta, IFNgamma and TNFalpha mRNA was evaluated in PBC (n = 15) and control livers (n = 21) using semi-quantitative reverse transcriptase-PCR.
  
  
  RESULTS
  In PBC and CVH livers, the amounts of infiltrating Foxp3+Tregs in portal tracts were in parallel with the degree of portal inflammation irrespective of disease. The infiltration of Foxp3+Tregs into portal tracts with CNSDC in PBC was foremost in comparison with inflamed portal tracts in CVH or those without CNSDC in PBC (p<0.05). Focally, Tregs infiltrated into the biliary epithelial layer at the site of CNSDC. The level of Foxp3, IL-10 and TGFbeta mRNA expression was high in PBC compared with normal livers (p<0.05). IFNgamma and TNFalpha mRNA was high in early PBC and CVH livers.
  
  
  CONCLUSIONS
  Results of this evaluation of Foxp3+Tregs do not suggest that the reduced regulatory function accounts for the development of CNSDC in PBC.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Seiko
authors.initials: S
authors.lastname: Sawada
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology*; D001653:Bile Ducts, Intrahepatic / Q000276:immunology*; D002761:Cholangitis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006521:Hepatitis, Chronic / Q000276:immunology; D006525:Hepatitis, Viral, Human / Q000276:immunology; D006801:Humans; D008099:Liver / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger