Association of CD4+CD25+Foxp3+ regulatory T cells with chronic activity and viral clearance in patients with hepatitis B.
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-beta 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.
Yang
Guilin
G
Joint Immunology Laboratory, Institute of Health Sciences, Shanghai Jiao-Tong University School of Medicine, Chinese Academy of Sciences, Shanghai, China.
Liu
Ailian
A
Xie
Qing
Q
Guo
Taylor B
TB
Wan
Bing
B
Zhou
Boping
B
Zhang
Jingwu Z
JZ
D000328:Adult; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D006513:Hepatitis B e Antigens / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology*; D016212:Transforming Growth Factor beta / Q000097:blood
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006513:Hepatitis B e Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta