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Digestive Diseases and Sciences

, Volume 59, Issue 7, pp 1475–1483 | Cite as

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

  • Jie LiEmail author
  • Jun Shi
  • Wanhua Ren
  • Wei Wu
  • Zhi Chen
Original Article

Abstract

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.

Keywords

Hepatitis B virus Antigen-specific CD4+CD25+Foxp3+ regulatory T cells Regulation IL-17-secreting T cells 

Notes

Acknowledgments

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

None.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Infectious DiseaseShandong Provincial Hospital affiliated to Shandong UniversityJinanChina
  2. 2.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated HospitalZhejiang UniversityHangzhouChina

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