In this study, we found a higher frequency of CD4+CXCR5+ TFH cells in IA patients and increased frequency of ICOS-, PD-1-expressing CD4+CXCR5+ in CHB patients. Our data support the notion http://www.selleckchem.com/products/wortmannin.html that TFH cells can circulate in peripheral blood [21]. The increased frequency of TFH cells may reflect active immune responses because TFH cells are crucial for antigen-specific B cell development and humoral responses against virus infection. Indeed, TFH cells have been thought to be resting memory TH cells [21]. However, we found that the frequency of CD4+CXCR5+ TFH cells was correlated negatively with the concentrations of serum HBeAb in CHB patients and that treatment with adefovir dipivoxil reduced the frequency of CD4+CXCR5+ TFH cells, but increased the levels of serum HBeAb, accompanied by increased levels of serum Th1 cytokines in drug-responding patients.

Apparently, high frequency of TFH cells is associated with a poor immunity against HBV infection. Alternatively, the increased frequency of peripheral blood TFH cells may stem from the altered distribution of Th1 and Th2 cells due to their infiltration in the target organs [22], [23]. However, we found that the percentages of splenic and liver CD4+CXCR5+ TFH cells in HBV-transgenic mice were significantly higher than that of wild-type mice, indicating that CD4+CXCR5+ TFH cells also migrated into the target organ in this model. More importantly, we found a positive correlation between the percentages of peripheral blood CD4+CXCR5+ TFH cells and the concentrations of serum AST in IA patients.

This positive correlation further suggests that TFH cells are associated with the HBV-related damages in the liver and indicates that the frequency of TFH cells may be another valuable biomarker (in addition to AST, ALT and HBV DNA loads) for distinguishing CHB patients at IA from IT phase. The high frequency of TFH cells may be a valuable biomarker for the evaluation of immune status in CHB patients at clinic. Notably, there was no significant correlation of the frequency of CD4+CXCR5+ TFH cells with the levels of serum ALT in IA patients. This may come from the population heterogeneity and small sample size in this study. Adefovir dipivoxil is a potent antiviral reagent, and treatment with adefovir dipivoxil can effectively inhibit the replication of HBV in the majority of CHB patients.

Our previous studies have shown that treatment with adefovir dipivoxil enhanced T cell immunity, which was associated with the inhibition of HBV replication in CHB patients [22], [23]. In this study, we further examined the impact of treatment Brefeldin_A with adefovir dipivoxil on systemic cytokine responses and found that treatment with adefovir dipivoxil significantly elevated the concentrations of serum IL-2 and IFN-��, but did not affect the levels of serum IL-4, IL-6, IL-10, IL-21, and TNF-�� in drug-responding patients.