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.
Shirin Nkongolo, Deeqa Mahamed, Adrian Kuipery, Juan D. Sanchez Vasquez, Samuel C. Kim, Aman Mehrotra, Anjali Patel, Christine Hu, Ian McGilvray, Jordan J. Feld, Scott Fung, Diana Chen, Jeffrey J. Wallin, Anuj Gaggar, Harry L.A. Janssen, Adam J. Gehring
Usage data is cumulative from August 2023 through August 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 2,259 | 518 |
403 | 166 | |
Figure | 729 | 12 |
Table | 70 | 0 |
Supplemental data | 151 | 32 |
Citation downloads | 72 | 0 |
Totals | 3,684 | 728 |
Total Views | 4,412 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.