Pathogenic CD8 T cells defined by longitudinal liver sampling in chronic hepatitis B patients starting antiviral therapy
Nkongolo, S.; Mahamed, D.; Kuipery, A.; Sanchez Vasquez, J. D.; Kim, S. C.; Mehrotra, A.; Patel, A.; Hu, C.; McGilvray, I.; Feld, J. J.; Fung, S.; Chen, D.; Wallin, J. J.; Gaggar, A.; Janssen, H. L. A.; Gehring, A. J.
Show abstract
Accumulation of activated immune cells results in non-specific hepatocyte killing in chronic hepatitis B (CHB), leading to fibrosis and cirrhosis. We enrolled 15 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 non-specific 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.
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