Naturally-occurring regulatory T cells are increased in inflamed portal tracts with cholangiopathy in primary biliary cirrhosis.
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.
Sasaki
Motoko
M
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Ikeda
Hiroko
H
Sawada
Seiko
S
Sato
Yasunori
Y
Nakanuma
Yasuni
Y
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*
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger