Abstract
BackgroundT follicular helper (TFH) cells are a special subpopulation of T helper cells and can regulate humoral immune responses. This study examined whether the frequency of CD4+CXCR5+ TFH cells could be associated with active immunity in chronic hepatitis B (CHB) patients.Methodology and FindingsThe frequencies of peripheral blood CD4+CXCR5+ TFH cells, inducible T cell costimulator (ICOS), and/or programmed death 1 (PD-1) positive CD4+CXCR5+ TFH cells in immune-active (IA), immune-tolerant (IT) CHB, and healthy controls (HC) were characterized by flow cytometry analysis. The effect of adevofir dipivoxil treatment on the frequency of CD4+CXCR5+ TFH cells, the concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-21, ALT, AST, HBsAg, HBsAb, HBeAg, HBeAb and HBV loads in IA patients were determined. The potential association of the frequency of CD4+CXCR5+ TFH cells with clinical measures was analyzed. In addition, the frequency of splenic and liver CD4+CXCR5+ TFH cells in HBV-transgenic mice was examined. We found that the frequency of CD4+CXCR5+ TFH cells in IA patients was significantly higher than that of IT patients and HC, and the percentages of CD4+CXCR5+ TFH in IA patients were positively correlated with AST. Furthermore, the percentages of ICOS+, PD-1+, and ICOS+PD-1+ in CD4+CXCR5+ TFH cells in CHB patients were significantly higher than that of HC. Treatment with adefovir dipivoxil reduced the frequency of CD4+CXCR5+ TFH, PD-1+CD4+CXCR5+ TFH cells and the concentrations of HBsAg and HBeAg, but increased the concentrations of HBsAb, HBeAb, IL-2 and IFN-γ in IA patients. Moreover, the frequency of splenic and liver CD4+CXCR5+ TFH cells in HBV-transgenic mice was higher than that of wild-type controls.ConclusionsThese data indicate that CD4+CXCR5+ TFH cells may participate in the HBV-related immune responses and that high frequency of CD4+CXCR5+ TFH cells may be a biomarker for the evaluation of active immune stage of CHB patients.
Highlights
HBV infection is a global health concern and an economical burden, affecting approximately 400 million people worldwide [1]
These data indicate that CD4+CXCR5+ T follicular helper (TFH) cells may participate in the HBV-related immune responses and that high frequency of CD4+CXCR5+ TFH cells may be a biomarker for the evaluation of active immune stage of chronic hepatitis B (CHB) patients
We found a high frequency of TFH cells in CHB patients at IA stage, which was positively associated with the levels of serum AST in this population
Summary
HBV infection is a global health concern and an economical burden, affecting approximately 400 million people worldwide [1]. Many patients infected with HBV progress into chronic hepatitis B (CHB) and can develop end-stage consequences (cirrhosis and hepatocellular carcinoma) [1]. There are about 130 million patients with HBV infection and 20% of them develop CHB in China [1]. During the HBV-infection, the interaction between replicating noncytopathic virus and dysregulatory host antiviral immunity determines the outcome [2]. Previous studies indicate that dynamic interactions between the virus, hepatocytes, and the host immune system may determine viral persistence and disease progression, which are displayed in distinct successive phases [4]. This study examined whether the frequency of CD4+CXCR5+ TFH cells could be associated with active immunity in chronic hepatitis B (CHB) patients
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