Lebossé, F;
Gudd, C;
Tunc, E;
Singanayagam, A;
Nathwani, R;
Triantafyllou, E;
Pop, O;
... Khamri, W; + view all
(2019)
CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction.
EBioMedicine
, 49
pp. 258-268.
10.1016/j.ebiom.2019.10.011.
Preview |
Text
CD8+T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction.pdf - Published Version Download (2MB) | Preview |
Abstract
BACKGROUND: Cirrhosis-associated immune dysfunction (CAID) contributes to high sepsis risk in patients with chronic liver disease. Various innate and; to a lesser extent; adaptive immune dysfunctions have been described as contributors to CAID leading to immune-paresis and impaired anti-microbial response in cirrhosis. In this study, we examined the phenotype of CD8+T cells in chronic liver disease with the aim to evaluate changes that might contribute to impaired immune responses. METHODS: Sixty patients with cirrhosis were prospectively recruited for this study. CD8+T cells from peripheral blood, ascites and liver explants were characterized using flow cytometry and immunohistochemistry, respectively. The transcriptional signature of flow-sorted HLA-DR+CD8+T cells was performed using Nanostring™ technology. HLA-DR+CD8+T cells interactions with PBMCs and myeloid cells were tested in vitro. FINDINGS: Peripheral CD8+T cells from cirrhotic patients displayed an altered phenotype characterized by high HLA-DR and TIM-3 surface expression associated with concomitant infections and disease severity, respectively. Paired peritoneal CD8+T cells expressed more pronounced levels of HLA-DR and PD-1 compared to peripheral CD8+T cells. HLA-DR+CD8+T cells were enriched in cirrhotic livers compared to controls. TIM-3, CTLA-4 and PD-1 levels were highly expressed on HLA-DR+CD8+T cells and co-expression of HLA-DR and PD1 was higher in patients with poor disease outcomes. Genes involved in cytokines production and intracellular signalling pathways were strongly down-regulated in HLA-DR+CD8+T cells. In comparison to their HLA-DR- counterparts, HLA-DR+CD8+T cells promoted less proliferation of PBMCs and induced phenotypic and functional dysfunctions in monocytes and neutrophils in vitro. INTERPRETATION: In patients with cirrhosis, CD8+T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID. FUND: This work was supported by Medical Research Council, the Rosetrees Charitable Trust, Robert Tournut 2016 grant (Sociéte Nationale Française de GastroEntérologie), Gilead® sciences, and NIHR Imperial Biomedical Research Centre.
| Type: | Article |
|---|---|
| Title: | CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ebiom.2019.10.011 |
| Publisher version: | https://doi.org/10.1016/j.ebiom.2019.10.011 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | CD8(+)T cells, Chronic liver disease, Cirrhosis-associated immune dysfunction |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10091037 |
Archive Staff Only
 |
View Item |
