Abstract
BackgroundBlood CXCR5+CD4+ T cells are defined as circulating T follicular helper (TFH) cells, which is required for effective humoral immunity. This study aimed to investigate the role of circulating TFH cells in patients with chronic hepatitis B virus (CHB) infection.MethodsThe frequency and phenotype of circulating TFH cells were monitored by flow cytometry in CHB patients and in healthy controls (HC). The expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA was analyzed using real-time PCR. Serum HBsAg, HBeAg, HBeAb, HBV DNA loads, ALT and AST were determined. The potential association of the frequency of TFH cells and their surface markers with clinical parameters was assessed.ResultsThe frequency of CXCR5+CD4+ T cells was increased in CHB patients and positively correlated with ALT and AST but not with HBV DNA loads. Moreover, an expansion of ICOS-, PD-1-, CD40L-, and IL-21R-expressing TFH cells occurred in CHB patients, but failed to correlate with ALT, AST and HBV DNA loads. Interestingly, the frequency of CXCR5+CD4+ T cells and ICOS+CXCR5+CD4+ T cells was significantly higher in HBeAg positive CHB patients than in HC. Additionally, the percentages of CXCR5+CD4+ T cells were positively correlated with AST, and ICOS-expressing CXCR5+CD4+ T cells were negatively correlated with HBV DNA loads. No significant differences in the frequency of CXCR5+CD4+ T cells were observed between inactive carrier (IC) patients and healthy controls. However, ICOS-, PD-1-, CD40L-expressing TFH cells were increased in IC patients and positively correlated with AST. Furthermore, the expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA in TFH cells was higher in CHB patients than in HC.ConclusionsThese data demonstrate that circulating TFH cells may participate in HBV-related immune responses. In addition to the frequency of TFH cells, the phenotype of these cells plays an important role in CHB patients.
Highlights
350 million people worldwide are carriers of hepatitis B virus (HBV), and half a million to 1 million of these carriers die from liver diseases each year [1]
The subjects were divided into the following groups according to AASLD guidelines [18]: HBeAg-positive chronic hepatitis B (HBeAg + chronic hepatitis B virus (CHB)) (n = 14); immune tolerant carrier (IT) (n = 8); inactive carrier (IC) (n = 10); and HBeAg-negative chronic hepatitis B (HBeAg- CHB) (n = 6)
The patients with chronic HBV infection were comparable to the healthy controls with respect to sex and age
Summary
350 million people worldwide are carriers of hepatitis B virus (HBV), and half a million to 1 million of these carriers die from liver diseases each year [1]. Therapeutic management of chronic hepatitis B patients can stop or slow the progression of the disease and reduce complications, but it is impossible to eradicate HBV and reverse liver damage [1,2]. The outcome of infection and the pathogenesis of liver disease are determined by Antibody production by B cells is critical for the clearance of pathogens and for the establishment of long-term humoral immunity [5]. T follicular helper (TFH) cells are the major CD4+ T cell subset that is essential for full B cell responses, including germinal center reactions, isotype class switching, and antibody affinity maturation [6]. Blood CXCR5+CD4+ T cells are defined as circulating T follicular helper (TFH) cells, which is required for effective humoral immunity. This study aimed to investigate the role of circulating TFH cells in patients with chronic hepatitis B virus (CHB) infection
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