Transcriptional and functional HBV-specific CD8 T cell changes from disease to functional cure in HBeAg-negative chronic hepatitis B
Exhausted HBV-specific CD8 T cells in chronic HBV infection are not a homogeneous population but comprise distinct subsets with differing capacities to control infection. This study identifies: (i) a transcriptional continuum of HBV-specific CD8 T-cell subsets spanning exhaustion to memory differentiation, reflecting disease progression and recovery in HBeAg-negative CHB; (ii) a core CD8 T-cell exhaustion gene signature characterized by progressively increased expression from memory-oriented to exhaustion-oriented subsets during active and resolution phases of disease; and (iii) the ability of targeted modulation of deregulated genes to restore antiviral CD8 T-cell function, with implications for the development of novel immune-based anti-HBV therapies. Overall, these findings advance our understanding of CD8 T-cell heterogeneity in chronic HBV infection and identify molecular targets for immunomodulatory strategies aimed at restoring CD8 T-cell functionality and achieving functional cure.
Authors
- Valentina Reverberi (ORCID: https://orcid.org/0000-0001-5703-1957)
- Anna Montali (ORCID: https://orcid.org/0000-0002-1134-7435)
- Diletta Laccabue (ORCID: https://orcid.org/0000-0002-8612-8042)
- Amalia Penna (ORCID: https://orcid.org/0000-0001-9663-1250)
- Paola Fisicaro (ORCID: https://orcid.org/0000-0003-3720-9214)
- Francesca Guerrieri (ORCID: https://orcid.org/0000-0002-2021-4394)
- Carolina Boni (ORCID: https://orcid.org/0000-0002-7630-5180)
- Massimo Levrero (ORCID: https://orcid.org/0000-0002-4978-0875)
- Dana Sambarino
- Marie‐Laure Plissonnier (ORCID: https://orcid.org/0000-0003-4879-4586)
- Carlo Ferrari (ORCID: https://orcid.org/0000-0002-5461-6842)
- Giuseppe Pedrazzi (ORCID: https://orcid.org/0000-0002-5971-2040)
- Arianna Alfieri
- Elisabetta Degasperi (ORCID: https://orcid.org/0000-0002-9899-4669)
- Gabriele Missale (ORCID: https://orcid.org/0000-0001-6691-8701)
- Andrea Vecchi (ORCID: https://orcid.org/0000-0001-8595-0651)
- Marzia Rossi (ORCID: https://orcid.org/0000-0003-4336-8502)
- Camilla Tiezzi (ORCID: https://orcid.org/0000-0001-5483-1908)
- Sara Doselli (ORCID: https://orcid.org/0009-0000-7533-0862)
- Benedetta Farina (ORCID: https://orcid.org/0000-0002-4696-7554)
- Elena Adelina Gabor
- Pietro Lampertico (ORCID: https://orcid.org/0000-0002-1026-7476)
- Alessio Pelagatti (ORCID: https://orcid.org/0009-0008-3884-2760)
Institutions
- Université Claude Bernard Lyon 1 (FR)
- University of Parma (IT)
- University of Milan (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Ospedale Maggiore (IT)
- Communauté urbaine de Lyon (FR)
- Hospices Civils de Lyon (FR)
- Ospedale di Parma (IT)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-12-04
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101705
- Primary Topic
- Hepatitis B Virus Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00