IL-21 Increases the Abundance of HBV-Specific CD8+ T CellsBecause CD8+ T cells are critical for successful immune control of HBV infection, we first analyzed the relationship between serum levels of IL-21 and the frequency of peripheral CD8+ T cells in CHB patients; there was no significant correlation between them (data not shown). Next, we investigated the effect of IL-21 on the abundance of CD8+ T cells in chronically HBV-infected patients. Exposure to IL-21 led to a marked increase in the global abundance of CD8+ T cells, especially the CD8high subset (Figure 2A). To examine whether IL-21 induced the proliferation of HBV-specific CD8+ T cells, we established CFSE-labeled in vitro cultures of PBMCs from HLA-A2+ patients with chronic HBV infection and cultured them with HBV core 18–27 peptide and recombinant human IL-21 (rhIL-21). Notably, we found that IL-21 significantly promoted the proliferation of HBV-specific CD8+ T cells (Figure 2B), and IL-21–mediated expansion showed a trend of a dose-dependent effect. Importantly, a significant increase in the frequency of HBV core–specific CD8+ T cells was also observed by MHC-I Streptamer staining (Figure 2C). Overall, the addition of IL-21 augmented the frequency of HBV-specific CD8+ T cells in PBMCs from patients with chronic HBV infection.