Franzese et al [27] have found that the frequencies of CD4+CD25+Treg cells showed no significant difference in patients with immunotolerant, chronic active and asymptomatic HBV infections, while the decrease in CD4+ CD25+ T cell frequency was found in patients with a flare-up of chronic hepatitis B. An in vitro study showed that depletion of the CD4+ CD25+ T cell population affected not only the expansion of HBV-specific CD8+ T cells but also their function [27]. This evidence concerns the gene CD4 and chronic hepatitis B virus infection.