Regulatory role of CD4(+)CD25 (+)Foxp3 (+) regulatory T cells on IL-17-secreting T cells in chronic hepatitis B patients.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Infectious Disease, Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China, lijier@sina.com.
Jie
J
Li
Jun
J
Shi
Wanhua
W
Ren
Wei
W
Wu
Zhi
Z
Chen
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism*
D015415:Biomarkers; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit