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.

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Keywords FoxP3, Hepatitis B virus, Liver, Regulatory T cells, Viral load
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Journal Clinical Immunology
Stoop, J.N, Claassen, M.A.A, Woltman, A.M, Binda, R.S, Kuipers, E.J, Janssen, H.L.A, … Boonstra, P.A. (2008). Intrahepatic regulatory T cells are phenotypically distinct from their peripheral counterparts in chronic HBV patients. Clinical Immunology, 129(3), 419–427. doi:10.1016/j.clim.2008.07.029