Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells
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 im...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2023-01-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI158903 |
| _version_ | 1797634495287918592 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shirin Nkongolo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:08:38Z |
| format | Article |
| id | doaj.art-3de81f98e7904dffa98ecc61f04fe620 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:08:38Z |
| publishDate | 2023-01-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-3de81f98e7904dffa98ecc61f04fe6202023-11-07T16:19:42ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-01-011331Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cellsShirin NkongoloDeeqa MahamedAdrian KuiperyJuan D. Sanchez VasquezSamuel C. KimAman MehrotraAnjali PatelChristine HuIan McGilvrayJordan J. FeldScott FungDiana ChenJeffrey J. WallinAnuj GaggarHarry L.A. JanssenAdam J. GehringAccumulation 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.https://doi.org/10.1172/JCI158903ImmunologyInfectious disease |
| spellingShingle | 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 Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells The Journal of Clinical Investigation Immunology Infectious disease |
| title | Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells |
| title_full | Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells |
| title_fullStr | Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells |
| title_full_unstemmed | Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells |
| title_short | Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells |
| title_sort | longitudinal liver sampling in patients with chronic hepatitis b starting antiviral therapy reveals hepatotoxic cd8 t cells |
| topic | Immunology Infectious disease |
| url | https://doi.org/10.1172/JCI158903 |
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