Regulatory Role of CD4+CD25+Foxp3+ Regulatory T Cells on IL-17-Secreting T Cells in Chronic Hepatitis B Patients
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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 ± 0.58 vs. 1.08 ± 0.36 %; P < 0.01) and Treg cells (8.92 ± 4.11 vs. 6.45 ± 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.
KeywordsHepatitis B virus Antigen-specific CD4+CD25+Foxp3+ regulatory T cells Regulation IL-17-secreting T cells
This work is supported by the National Natural Science Fund (No. 81201288), the State S&T Projects of 12th Five Year (No. 2012ZX10002003-004-007) and the Excellent Young Scientist Foundation of Shandong Province (No. 2008BS03014).
Conflict of interest
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