HBV Core-specific CD4+ T cells correlate with sustained viral control upon off-treatment in HBeAg-positive chronic hepatitis B patients.
Antiviral Res
; 213: 105585, 2023 05.
Article
em En
| MEDLINE
| ID: mdl-36963665
BACKGROUND & AIMS: Treatment with nucleos(t)ide analogue (NA) efficiently suppresses viral replication in patients with chronic HBV infection, yet HBV relapses frequently upon NA withdrawal; the detailed immunomodulatory compounds for sustained viral control of HBV upon NA interruption have yet to be fully clarified. This study aimed to elucidate the role of T cells specific for distinct HBV peptides in sustained response upon discontinuation of antiviral treatment. METHODS: A total of 48 patients with HBeAg-positive chronic hepatitis B receiving NA treatment and withdrawal were included longitudinally in a retrospective and prospective cohort. Enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) assays were performed to detect IFN-γ producing HBV-specific T cells following stimulation with overlapping peptides covering the whole HBV genome after 10 days of in vitro expansion. RESULTS: ICS assays revealed that T cells specific for HBV Core and Polymerase induced more robust IFN-γ responses compared to Envelope and HBx. Notably, at the time of NA discontinuation, the intensity and breadth of HBV Core peptides-induced responses, predominately targeted by CD4+ T cells but not CD8+ T cells, were associated with sustained viral control upon off-treatment. Further exploration of longitudinal features in patients with sustained viral control revealed that the breadth of HBV-specific T cell responses does not increase following treatment cessation. CONCLUSION: This report emphasizes the essential role of HBV Core-specific CD4+ T cells in sustained response after therapy withdrawal, indicating it is a potential candidate for immunotherapeutic approaches in chronic HBV patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatite B Crônica
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article