Association of CD4+CD25+Foxp3+ regulatory T cells with chronic activity and viral clearance in patients with hepatitis B

Abstract

Chronic activity of hepatitis B is thought to involve aberrant immune tolerance of unknown mechanism. In this study, we examined the role of CD4+CD25+Foxp3+ regulatory T cells in disease activity and viral clearance in hepatitis B. Patients with chronic active hepatitis B (CAH) and asymptomatic HBV carriers (AsC) exhibited a significantly high frequency of CD4+ CD25+Foxp3+ T cells as opposed to that of controls and resolved HBV infection. These CD4+ CD25+ T cells expressed an elevated level of Foxp3 and displayed increased inhibitory activity towards both CD4+ CD25- and CD8+ effector cells. They were found to accumulate in liver biopsy tissue of CAH patients as opposed to controls. The frequency of CD4+ CD25+ Foxp3+ T cells correlated positively with hepatitis B envelope (HBe) antigen status and serum HBV DNA copy numbers and had a converse relationship with HBe antibody status in patients with CAH and AsC. It was evident that in these patients, the increased frequency of CD4+CD25+ Foxp3+ T cells was associated with serum levels of transforming growth factor-β known to promote peripheral conversion of CD4+ CD25- T cells to CD4+ CD25+ Foxp3+ regulatory T cells. The findings provide new insights into the role of CD4+CD25+ Foxp3+ regulatory T cells in chronic activity and viral clearance in chronic hepatitis B. © 2007 Oxford University Press.