Hepatitis B e-antigen persistency is associated with the properties of HBV-specific CD8 T cells in CHB patients

J Clin Immunol. 2011 Apr;31(2):195-204. doi: 10.1007/s10875-010-9483-5. Epub 2010 Dec 1.

Abstract

To investigate the correlation between the HBeAg and the properties of HBV-specific CD8 T cells, as well as liver injury, serum HBV markers, liver histology, the frequency and phenotypic characteristics of CD4(+)CD25(+) Treg and HBV-pentamer(+) CD8 T cells were measured. No significant differences between the median serum ALT levels, the frequency and Foxp3 expression of CD4(+)CD25(+) Treg, and liver fibrosis were observed. Higher HBV DNA levels in HBeAg(+) patients were observed, while liver necroinflammation was more severe in HBeAg(-) patients. Differences in HBV-pentamer(+) T cell frequency were not significant, but increased PD-1 and CTLA-4 expression on HBV-specific CD8 T cells was seen in the HBeAg(+) group. HBV-peptide stimulation with anti-PD-L1 and anti-CTLA-4 significantly increased the proliferation in PBMCs from both groups, but enhanced IFN-γ production only in the HBeAg(+) patients. Therefore, HBeAg persistency in CHB patients probably increased the expression of PD-1 and CTLA-4 on HBV-specific CD8 T cells, which may be associated with the low intensity of T cell responses and high HBV DNA load.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology*
  • DNA, Viral / blood
  • Epitopes / immunology
  • Female
  • Forkhead Transcription Factors / immunology
  • Hepatitis B e Antigens / blood
  • Hepatitis B e Antigens / immunology*
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / enzymology
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • RNA, Messenger / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Young Adult

Substances

  • DNA, Viral
  • Epitopes
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Hepatitis B e Antigens
  • RNA, Messenger
  • Alanine Transaminase