Regulatory Role of CD4+CD25+Foxp3+ Regulatory T Cells on IL-17-Secreting T Cells in Chronic Hepatitis B Patients

Both interleukin (IL)-17-secreting CD4(+) T (Th17) and CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells have been shown to be associated with disease progression or liver damage in chronic hepatitis B (CHB) patients. However, the relationship between Treg cells and IL-17-secreting T cells in hepatitis B virus (HBV) infections is unclear. The frequencies of Treg cells and IL-17-secreting T cells in hepatitis B e antigen (HBeAg)-positive CHB patients and healthy subjects were measured by flow cytometric analysis. The role of Treg cells on the differentiation of Ag-specific IL-17-secreting T cells was determined by removing the Treg cells from peripheral blood mononuclear cells (PBMCs) in HBeAg-positive CHB patients. The frequencies of both Th17 (1.71 +/- A 0.58 vs. 1.08 +/- A 0.36 %; P < 0.01) and Treg cells (8.92 +/- A 4.11 vs. 6.45 +/- A 1.56 %; P < 0.01) were increased in the peripheral blood of HBeAg-positive CHB patients compared with healthy controls, but in not the IL-17-secreting CD8(+) T (Tc17) cells. The frequency of Treg cells was significantly associated with that of Th17 cells (r = 0.625, P = 0.001) in CHB patients. Spearman analysis showed a positive correlation between the frequency of Treg cells and HBV DNA load (r = 0.508, P = 0.008), as well as between the frequency of Th17 cells and serum alanine aminotransferase level (r = 0.516, P = 0.007). The deletion of Treg cells significantly enhanced both Th17 and Tc17 cell development in PBMCs following recombinant HBV core antigen stimulation. Our data indicate a clear inverse relationship between Th17 cells and Treg cells and that Treg cells can inhibit Th17 cell development in CHB patients.