Imperial College London
Portrait Picture

Dr Evangelos Triantafyllou

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Lecturer in Liver Immunology
 
 
 
//

Contact

 

e.triantafyllou Website

 
 
//

Location

 

10.N12ACommonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Khamri:2021:10.1136/gutjnl-2021-324071,
author = {Khamri, W and Gudd, C and Liu, T and Nathwani, R and Krasniqi, M and Azam, S and Barbera, T and Trovato, FM and Possamai, LA and Triantafyllou, E and Castro, Seoane R and Lebosse, F and Singanayagam, A and Kumar, N and Bernsmeier, C and Mukherjee, S and McPhail, MJW and Weston, CJ and Antoniades, CG and Thursz, MR},
doi = {10.1136/gutjnl-2021-324071},
journal = {Gut},
pages = {1192--1202},
title = {Suppressor CD4+ T cells expressing HLA-G are expanded in the peripheral blood from patients with acute decompensation of cirrhosis},
url = {http://dx.doi.org/10.1136/gutjnl-2021-324071},
volume = {71},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Objective Identifying components of immuneparesis, a hallmark of chronic liver failure, is crucial for our understanding of complications in cirrhosis. Various suppressor CD4+ T cells have been established as potent inhibitors of systemic immune activation. Here, we establish the presence, regulation and mechanism of action of a suppressive CD4+ T cell subset expressing human leucocyte antigen G (HLA-G) in patients with acute decompensation of cirrhosis (AD).Design Flow cytometry was used to determine the proportion and immunophenotype of CD4+HLA-G+ T cells from peripheral blood of 20 healthy controls (HCs) and 98 patients with cirrhosis (28 with stable cirrhosis (SC), 20 with chronic decompensated cirrhosis (CD) and 50 with AD). Transcriptional and functional signatures of cell-sorted CD4+HLA-G+ cells were delineated by NanoString technology and suppression assays, respectively. The role of immunosuppressive cytokine interleukin (IL)-35 in inducing this population was investigated through in vitro blockade experiments. Immunohistochemistry (IHC) and cultures of primary human Kupffer cells (KCs) were performed to assess cellular sources of IL-35. HLA-G-mediated T cell suppression was explored using neutralising antibodies targeting co-inhibitory pathways.Results Patients with AD were distinguished by an expansion of a CD4+HLA-G+CTLA-4+IL-35+ immunosuppressive population associated with disease severity, clinical course of AD, infectious complications and poor outcome. Transcriptomic analyses excluded the possibility that these were thymic-derived regulatory T cells. IHC analyses and in vitro cultures demonstrate that KCs represent a potent source of IL-35 which can induce the observed HLA-G+ phenotype. These exert cytotoxic T lymphocyte antigen-4-mediated impaired responses in T cells paralleled by an HLA-G-driven downregulation of T helper 17-related cytokines.Conclusion We have identified a cytokine-driven peripherally derived suppressive population that may contr
AU  - Khamri,W
AU  - Gudd,C
AU  - Liu,T
AU  - Nathwani,R
AU  - Krasniqi,M
AU  - Azam,S
AU  - Barbera,T
AU  - Trovato,FM
AU  - Possamai,LA
AU  - Triantafyllou,E
AU  - Castro,Seoane R
AU  - Lebosse,F
AU  - Singanayagam,A
AU  - Kumar,N
AU  - Bernsmeier,C
AU  - Mukherjee,S
AU  - McPhail,MJW
AU  - Weston,CJ
AU  - Antoniades,CG
AU  - Thursz,MR
DO  - 10.1136/gutjnl-2021-324071
EP  - 1202
PY  - 2021///
SN  - 0017-5749
SP  - 1192
TI  - Suppressor CD4+ T cells expressing HLA-G are expanded in the peripheral blood from patients with acute decompensation of cirrhosis
T2  - Gut
UR  - http://dx.doi.org/10.1136/gutjnl-2021-324071
UR  - https://gut.bmj.com/content/71/6/1192
UR  - http://hdl.handle.net/10044/1/90704
VL  - 71
ER  -
Download