Mechanism of T cell hyporesponsiveness to HBcAg is associated with regulatory T cells in chronic hepatitis B

Yasuteru Kondo, Koju Kobayashi, Yoshiyuki Ueno, Masaaki Shiina, Hirofumi Niitsuma, Noriatsu Kanno, Tomoo Kobayashi, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Aim: To study the mechanisms of hyporesponsiveness of HBV-specific CD4+ T cells by testing TH1 and TH2 commitment and regulatory T cells. Methods: Nine patients with chronic hepatitis B were enrolled. Peripheral blood mononuclear cells were stimulated with HBcAg or HBsAg to evaluate their potential to commit to TH1 and TH2 differentiation. HBcAg-specific activity of regulatory T cells was evaluated by staining with antibodies to CD4, CD25, CTLA-4 and interleukin-10. The role of regulatory T cells was further assessed by treatment with anti-interleukin-10 antibody and depletion of CD4+CD25+ cells. Results: Level of mRNAs for T-bet, IL-12R β2 and IL-4 was significantly lower in the patients than in healthy subjects with HBcAg stimulation. Although populations of CD4+CD25highCTLA-4+ T cells were not different between the patients and healthy subjects, IL-10 secreting cells were found in CD4+ cells and CD4+CD25+ cells in the patients in response to HBcAg, and they were not found in cells which were stimulated with HBsAg. Addition of anti-IL-10 antibody recovered the amount of HBcAg-specific TH1 antibody compared with control antibody (P < 0.01, 0.34% ± 0.12% vs 0.15% ± 0.04%). Deletion of CD4+CD25+ T cells increased the amount of HBcAg-specific TH1 antibody when compared with lymphocytes reconstituted using regulatory T cells (P < 0.01, 0.03% ± 0.02% vs 0.18% ± 0.05%). Conclusion: The results indicate that the mechanism of T cell hyporesponsiveness to HBcAg includes activation of HBcAg-induced regulatory T cells in contrast to an increase in TH2-committed cells in response to HBsAg.

Original languageEnglish
Pages (from-to)4310-4317
Number of pages8
JournalWorld Journal of Gastroenterology
Volume12
Issue number27
DOIs
Publication statusPublished - 2006 Jul 21

Keywords

  • FOXP3
  • Hepatitis B virus
  • IL-10
  • Regulatory T cells
  • TH1

ASJC Scopus subject areas

  • Gastroenterology

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