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Objective T follicular helper (TFH) cells are a special subpopulation of T helper cells and can regulate antibodyproduction by B cells.Few studies have focused on the role of TFH cells in chronic hepatitis C virus (HCV) infection currently.Our study aimed to explore the role of TFH cells in chronic HCV infection.Metthods The percentage of perpheral blood CD4+CXCR5+ TFH cells was assessed by flow cytometry (FACS).The concentration of serum IL-21 was determinde by ELISA assay.Results The percentage of peripheral blood CD4+CXCR5+ Tfh cells in total CD4+ cells in HCV-infected patients (22.3%) was significantly higher than that in healthy controls (8.9%;P < 0.01).The percentage of ICOS+PD-1 +CD4+CXCR5+ Tfh cells in HCV-infected patients also increased.Intracellular staining revealed that the ratio of IL-21 secreted by CD4+ T cells in chronic HCV-infected patients (2.8%)was higher than that in healthy controls(0.8%;P<0.01).The concentration of serum IL-21 was also increased in HCV patients,Further analysis showed that the expression of IL-21 in HCV patients was significantly higher in those with a low HCV RNA load (log 10 HCV RNA < 6) than that in the patients with a high HCV RNA load (log10 HCV RNA > 6).Conclusion CD4+CXCR5+Tfh cells might participate in the HCV-related immunity.