Circulating CXCR5+CD8+T cells maintain decent antiviral abilities and are associated with treatment response in patients with CHBWe further investigated the relationship between circulating CXCR5+CD8+T cells and treatment response in patients with CHB. Interestingly, the levels of HBV DNA at week 52 showed an inverse correlation with the frequency of CXCR5+CD8+T cells at baseline and at week 12 (Fig. 2A). Notably, the frequency of CXCR5+CD8+T cells was significantly higher in CR patients than in NCR patients both at baseline and at week 12. Moreover, a significantly higher frequency of IFN-γ-producing CXCR5+CD8+T cells was detected in CR patients than in NCR patients both at baseline and at week 24, while no significant differences were observed at week 12 and week 52 (Fig. 2B). We then compared the antiviral efficacy between circulating CXCR5+CD8+ and CXCR5−CD8+T cells. Relative to that from CXCR5−CD8+T cells, a decreased level of Granzyme B but an enhanced level of IFN-γ was detected in the supernatant from CXCR5+CD8+T cells after in vitro stimulation (Fig. 2C and 2D). Next, the supernatant obtained from the sorted cells was added to HBV-producing HepG2.2.15 cells, respectively. Notably, we found that the addition of supernatant from the CXCR5+ subset resulted in significantly decreased expression of HBsAg and HBeAg (Fig. 2E). Taken together, these data demonstrated that the less exhausted CXCR5+CD8+T cells exerted antiviral effects predominantly through a non-cytolytic mechanism and suggested that they may contribute to HBV control.