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

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.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.Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic DNA virus that is capable of inducing necro-inflammatory liver disease with varying severity. Persistent infection by HBV is often associated with chronic liver disease, which can further lead to the development of cirrhosis and hepatocellular carcinoma [1,2]. While many of the underlying mechanisms of HBV infection progression have been described, the complex array of pathogen-host interactions is not yet fully understood. A growing body of recent evidence has suggested that CD4+CD25+Foxp3+ regulatory T cells (Tregs) may play an important role in the suppression of antiviral T cell responses during the chronic phases of HBV infection [3,4]. Some studies have demonstrated that HBV carriers have a higher frequency of Tregs in peripheral blood and liver than healthy controls or individuals with resolved infection, indicating that Tregs may contribut