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International Immunology Advance Access originally published online on December 20, 2006
International Immunology 2007 19(2):133-140; doi:10.1093/intimm/dxl130
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Guilin Yang1,2, Ailian Liu1, Qing Xie3, Taylor B. Guo1, Bing Wan1, Boping Zhou2 and Jingwu Z. Zhang1,4,5

1 Joint Immunology Laboratory of Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai Jiao-Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
2 Shenzhen Municipal Hospital of Infectious Diseases, Shenzhen, China
3 Department of Infectious Diseases, Rui-Jin General Hospital, Shanghai, China
4 Immunology Divsion, E-Institutes of Shanghai Universities, China
5 Present address: Institute of Health Sciences, 225 South Chongqing Road, Shanghai 200025, China

Correspondence to: J. Z. Zhang; E-mail: jzang{at}bcm.tmc.edu

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-ß 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.

Keywords: CD4+CD25+ regulatory T cells, hepatitis B, TGF-ß, transcription factor Foxp3

Transmitting editor: C. J. Paige


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