Expression Of Circulating TFH Cells In Patients With Chronic HBV Infection

Objective: This study aimed to investigate the role of circulating TFHcells in patients with chronic HBV infection through detecting thefrequency and phenotype of circulating TFH cells and assessing thepotential association of the frequency of circulating TFH cells and theirsurface markers with clinical parameters.Methods: The frequency and phenotype (i.e., ICOS, PD-1, CD40L,and IL-21R expression) of circulating TFH cells were monitored by flowcytometry in HBeAg-positive chronic hepatitis B (HBeAg+CHB), immunetolerant carrier (IT), inactive carrier (IC), and HBeAg-negative chronichepatitis B (HBeAg-CHB) patients and in healthy controls (HC). Theexpression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA wasanalyzed using real-time PCR. Serum HBsAg, HBeAg, HBeAb, HBVDNA loads, ALT and AST were determined. The potential association ofthe frequency of circulating TFH cells and their surface markers withclinical parameters was assessed.Results: The frequency of CXCR5+CD4+T cells was increased in patients with chronic HBV infection and positively correlated with serumlevels of ALT and AST but not with HBV DNA loads. Moreover, anexpansion of ICOS, PD-1, CD40L, and IL-21R-expressing CXCR5+CD4+Tcells occurred in patients with chronic HBV infection. However, thepercentages of ICOS+CXCR5+CD4+T cells, PD-1+CXCR5+CD4+T cells,CD40L+CXCR5+CD4+T cells, and IL-21R+CXCR5+CD4+T cells failed tocorrelate with serum levels of ALT, AST and HBV DNA loads.Interestingly, the frequency of CXCR5+CD4+T cells andICOS+CXCR5+CD4+T cells was significantly higher in HBeAg+CHBpatients than in HC. In addition, the percentages of CXCR5+CD4+T cells inHBeAg+CHB patients were positively correlated with AST, and theproportions of ICOS+CXCR5+CD4+T cells in HBeAg+CHB patients werenegatively correlated with HBV DNA loads. No significant differences inthe frequency of CXCR5+CD4+T cells were observed between IC patientsand healthy controls. However, the percentages of ICOS+CXCR5+CD4+Tcells, PD-1+CXCR5+CD4+T cells, and CD40L+CXCR5+CD4+T cells wereincreased in IC patients and positively correlated with AST. Furthermore,the expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA incirculating TFH cells was higher in patients with chronic HBV infectionthan in healthy controls.Conclusions: These data demonstrate that circulating TFH cells may participate in HBV-related immune responses. In addition to the frequencyof CXCR5+CD4+T cells, the phenotype of these cells plays an importantrole in patients with chronic HBV infection.