Expression of CD39 on FoxP3+ T regulatory cells correlates with progression of HBV infection

Background: Although it is known that regulatory T cells (Tregs) can suppress the function of effector T cells, and may contribute to impaired immune response, the precise role of Tregs during the course of hepatitis B virus (HBV) infection remains to be elucidated. A newly identified subset of the CD4(+) Foxp3(+) Tregs, the CD39(+) Tregs, has been associated with viral infections and autoimmune diseases. Therefore, we hypothesized that this discrete Treg subset may contribute to the chronic infection of HBV. Results: Initial characterization studies of healthy peripheral CD39(+)FoxP3(+)CD4(+) T cells revealed that the majority were CD45RA-Treg cells. Subsequent analysis of HBV-infected patients (38 asymptomatic HBV carriers (AsCs), 37 chronic active hepatitis B (CAH), 29 HBV-associated acute-on-chronic liver failure (ACLF)) and healthy individuals (25 controls) was conducted to assess association with HBV copy number and the liver injury marker alanine aminotransferase (ALT). A higher percentage of CD39(+) Tregs was detected within the population of FoxP3(+)CD4(+) T cells in peripheral blood of AsCs patients. Moreover, the percentage of CD39(+) Tregs was significantly less in CAH and ACLF patients. The increased proportions of circulating CD39(+) Tregs were positively correlated with serum viral load, but inversely correlated with serum ALT level. Conclusion: These findings not only suggest that CD39(+) Treg cells may be involved in HBV disease progression but also identify CD39(+) Tregs as a dynamic immune regulatory cell population that may represent a new target of immunomodulatory therapeutic interventions.