High Frequency of CD4+CXCR5+ TFH Cells in Patients with Immune-Active Chronic Hepatitis B

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.

CD4 T follicular helper cell dynamics during SIV infection

“…Notably, these levels of sCD14 were comparable to the levels during acute SIV infection ( Figure 6A). IL-6, a proinflammatory cytokine that is a critical regulator of TFH cells (19,21,22,37), is increased in HIV infection (38). In line with the sCD14 levels, we found significantly increased levels of plasma IL-6 in chronically SIV-infected RMs compared with those in noninfected animals ( Figure 6B).…”

The darker side of follicular helper T cells: from autoimmunity to immunodeficiency

“…T H -cell differentiation is polarized toward T FH cells to generate B-cell responses against infections. 36,37 These responses, if exaggerated by aberrant T FH -cell function, may also promote autoimmune diseases. A recent interesting study examined the role of T FH cells in the development of autoimmunity during chronic Salmonella infection in mice.…”

Role of interleukin-21 in HBV infection: friend or foe?

“…23 Peripheral blood CXCR5 1 CD4 1 T cells also participate in HBV-related immune responses. In a study by Feng et al, 44 immune active CHB patients had increased frequencies of peripheral blood CXCR5 1 CD4 1 T cells. Consistent with this observation, we recently found that both the overall and HBV-specific circulating CXCR5 1 CD4 1 T cells were expanded in chronic HBV infection, and a high frequency of this cell subset was associated with HBeAg seroconversion in both cross-sectional and longitudinal studies.…”