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[The phenotype and function of CD4+ CD25+ regulatory T cells in hepatitis B patients]

Jun-liang Fu1, Dong-ping Xu, Ming Shi

  • 1Research Center of Biological Therapy, the 302th Hospital of PLA, Beijing 100039, China.

Zhonghua Nei Ke Za Zhi
|November 1, 2006
PubMed

Insights

Chronic hepatitis B patients have more regulatory T cells (Treg) than acute hepatitis B patients. These Treg cells can suppress hepatitis B virus (HBV) specific immune responses in vitro, offering insights into HBV immunopathogenesis.

Area of Science:

  • Immunology
  • Hepatology
  • Virology

Background:

  • Hepatitis B virus (HBV) infection can lead to chronic liver disease.
  • Regulatory T cells (Treg) play a crucial role in immune homeostasis and tolerance.
  • The specific role of Treg cells in the immunopathogenesis of HBV infection requires further elucidation.

Purpose of the Study:

  • To investigate the frequency, phenotype, and function of CD4+ CD25 high regulatory T cells (Treg) in patients with acute hepatitis B (AHB) and chronic hepatitis B (CHB).

Main Methods:

  • Flow cytometry was used to analyze Treg frequency and phenotype (CD45RO, CD45RA, CD95, HLA-DR) in peripheral blood mononuclear cells (PBMCs) from AHB, CHB patients, and healthy controls.
  • Intracellular staining assessed cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) expression, while real-time RT-PCR detected Forkhead/winged helix transcription factor (FoxP3) mRNA.
  • The suppressive function of purified Treg cells on PBMC proliferation and interferon-gamma (IFN-γ) secretion was evaluated using [3H]-thymidine incorporation assays and ELISA, respectively.

Main Results:

  • Chronic hepatitis B patients exhibited a higher frequency of circulating CD4+ CD25 high Treg cells compared to acute hepatitis B patients (P < 0.05), with no significant difference compared to healthy controls.
  • CD4+ CD25 high Treg cells expressed high levels of CD45RO, HLA-DR, and CTLA-4, low levels of CD45RA, and specifically expressed FoxP3 mRNA.
  • Purified Treg cells demonstrated the ability to suppress the proliferation and IFN-γ secretion of autologous PBMCs, with a more pronounced suppressive effect observed when stimulated with HBV antigen compared to anti-CD3 antibody.

Conclusions:

  • Circulating Treg frequency is elevated in CHB patients compared to AHB patients, but similar to healthy individuals.
  • FoxP3 mRNA is specifically expressed in the CD4+ CD25+ cell population, confirming their regulatory T cell identity.
  • Treg cells possess the capacity to suppress HBV antigen-specific T cell responses in vitro, contributing to the understanding of Treg cells' role in hepatitis B immunopathogenesis.
Abstract

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