Imperial College London
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Dr Evangelos Triantafyllou

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Lecturer in Liver Immunology
 
 
 
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Contact

 

e.triantafyllou Website

 
 
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Location

 

10.N12ACommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lebosse:2019:10.1016/j.ebiom.2019.10.011,
author = {Lebosse, F and Gudd, C and Tunc, E and Singanayagam, A and Nathwani, R and Triantafyllou, E and Pop, O and Kumar, N and Mukherjee, S and Zheng, Hou T and Quaglia, A and Zoulim, F and Wendon, J and Dhar, A and Thursz, M and Antoniades, C and Khamri, W},
doi = {10.1016/j.ebiom.2019.10.011},
journal = {EBioMedicine},
pages = {258--268},
title = {CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction},
url = {http://dx.doi.org/10.1016/j.ebiom.2019.10.011},
volume = {49},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundCirrhosis-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.MethodsSixty 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.FindingsPeripheral 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.InterpretationIn patients with cirrhosis, CD8+ T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID.FundThis work was supported by Medical Res
AU  - Lebosse,F
AU  - Gudd,C
AU  - Tunc,E
AU  - Singanayagam,A
AU  - Nathwani,R
AU  - Triantafyllou,E
AU  - Pop,O
AU  - Kumar,N
AU  - Mukherjee,S
AU  - Zheng,Hou T
AU  - Quaglia,A
AU  - Zoulim,F
AU  - Wendon,J
AU  - Dhar,A
AU  - Thursz,M
AU  - Antoniades,C
AU  - Khamri,W
DO  - 10.1016/j.ebiom.2019.10.011
EP  - 268
PY  - 2019///
SN  - 2352-3964
SP  - 258
TI  - CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction
T2  - EBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2019.10.011
UR  - http://hdl.handle.net/10044/1/74505
VL  - 49
ER  -
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