Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells.
J Clin Invest
; 133(1)2023 01 03.
Article
in En
| MEDLINE
| ID: mdl-36594467
ABSTRACT
Accumulation of activated immune cells results in nonspecific hepatocyte killing in chronic hepatitis B (CHB), leading to fibrosis and cirrhosis. This study aims to understand the underlying mechanisms in humans and to define whether these are driven by widespread activation or a subpopulation of immune cells. We enrolled CHB patients with active liver damage to receive antiviral therapy and performed longitudinal liver sampling using fine-needle aspiration to investigate mechanisms of CHB pathogenesis in the human liver. Single-cell sequencing of total liver cells revealed a distinct liver-resident, polyclonal CD8+ T cell population that was enriched at baseline and displayed a highly activated immune signature during liver damage. Cytokine combinations, identified by in silico prediction of ligand-receptor interaction, induced the activated phenotype in healthy liver CD8+ T cells, resulting in nonspecific Fas ligand-mediated killing of target cells. These results define a CD8+ T cell population in the human liver that can drive pathogenesis and a key pathway involved in their function in CHB patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatitis B, Chronic
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Clin Invest
Year:
2023
Document type:
Article
Affiliation country:
Canadá