Hepatitis B envelope antigen increases Tregs by converting CD4+CD25 T cells into CD4CD25Foxp3 Tregs.

Hepatitis B virus (HBV) can establish a lifelong chronic infection in humans, leading to liver cirrhosis, liver failure and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) exhibit a weak virus-specific immune response. Regulatory T cells (Tregs) play a key role in regulating the immune response in patients with CHB. Patients with hepatitis B envelope antigen (HBeAg)-positive CHB harbored a higher percentage of Tregs in their peripheral blood than those with HBeAg-negative CHB. However, whether and how HBeAg manipulates the host immune system to increase the population of Tregs remains to be elucidated. The present manuscript describes a preliminary immunological study of HBeAg in a mouse model. Multiple potential CD4 T cell epitopes in HBeAg were identified using Immune Epitope Database consensus binding prediction. It was demonstrated that HBeAg treatment increased the numbers of Tregs in mouse spleens and . Furthermore, it was indicated that the HBeAg-mediated increase in Tregs occurred through the conversion of CD4CD25 T cells into CD4CD25Foxp3 Tregs. Additionally, study illustrated that HBeAg stimulated murine spleen cells to produce increased transforming growth factor-β, which is required to enable HBeAg to convert T cells into Tregs. The results of the present study may provide further evidence of the effect of HBeAg on Tregs and aid in the development of novel HBeAg-based immunotherapy for CHB.