title: Intrahepatic regulatory T cells are phenotypically distinct from their peripheral counterparts in chronic HBV patients.
abstract: Peripheral blood CD4+CD25+ regulatory T cells (Treg) prevent the development of strong HBV-specific T cell responses in vitro. In this study, we examined the phenotype of FoxP3+ regulatory T cells in the liver of patients with a chronic HBV infection. We showed that the liver contained a population of CD4+FoxP3+ cells that did not express CD25, while these cells were absent from peripheral blood. Interestingly, intrahepatic CD25-FoxP3+CD4+ T cells demonstrated lower expression of HLA-DR and CTLA-4 as compared to their CD25+ counterparts. Patients with a high viral load have a higher proportion of regulatory T cells in the liver, but not in blood, compared to patients with a low viral load. In conclusion, the intrahepatic Treg are phenotypically distinct from peripheral blood Treg. Our data suggest that the higher proportion of intrahepatic Treg observed in patients with a high viral load may explain the lack of control of viral replication.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jeroen N
authors.initials: JN
authors.lastname: Stoop
authors.forename: Mark A A
authors.initials: MA
authors.lastname: Claassen
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Woltman
authors.forename: Rekha S
authors.initials: RS
authors.lastname: Binda
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Renate G
authors.initials: RG
authors.lastname: van der Molen
authors.forename: Andre
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D060908:CTLA-4 Antigen; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000254:growth & development*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology* / Q000821:virology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004279:DNA, Viral; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens; D006513:Hepatitis B e Antigens; D053645:Interleukin-2 Receptor alpha Subunit