Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation

Jones, Nick; Cronin, James; Dolton, Garry; Panetti, Silvia; Schauenburg, Andrea J.; E., Sarah A.; Sewell, Andrew K.; Cole, David K.; Thornton, Cathy; Francis, Nigel

doi:10.3389/fimmu.2017.01516

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Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation

Nick Jones

, James Cronin

, Garry Dolton, Silvia Panetti, Andrea J. Schauenburg, Sarah A. E. Galloway, Andrew K. Sewell, David K. Cole, Cathy Thornton

, Nigel Francis

Frontiers in Immunology, Volume: 8, Issue: 1516

Swansea University Authors: Nick Jones , James Cronin , Cathy Thornton , Nigel Francis

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Copyright: © 2017 Jones, Cronin, Dolton, Panetti, Schauenburg, Galloway, Sewell, Cole, Thornton and Francis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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DOI (Published version): 10.3389/fimmu.2017.01516

Abstract

Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell recepto...

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Published in:	Frontiers in Immunology
ISSN:	1664-3224
Published:	2017
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa36275
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first_indexed	2017-10-26T13:34:23Z
last_indexed	2020-07-14T13:02:04Z
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T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell receptor (TCR) and peptides presented by human leukocyte antigens (pHLA). The role of TCR-pHLA interactions in modulating T-cell metabolism is unknown. Here for the first time we explore the relative contributions of the main metabolic pathways to functional responses in human CD4+ and CD8+ T-cells. Increased expression of hexokinase II accompanied by higher basal glycolysis is demonstrated in CD4+ T-cells; cytokine production in CD8+ T-cells is more reliant on oxidative phosphorylation. Using antigen-specific CD4+ and CD8+ T cell clones and altered peptide ligands we demonstrate that binding affinity tunes the underlying metabolic shift. 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E.</firstname><surname>Galloway</surname><order>6</order></author><author><firstname>Andrew K.</firstname><surname>Sewell</surname><order>7</order></author><author><firstname>David K.</firstname><surname>Cole</surname><order>8</order></author><author><firstname>Cathy</firstname><surname>Thornton</surname><orcid>0000-0002-5153-573X</orcid><order>9</order></author><author><firstname>Nigel</firstname><surname>Francis</surname><order>10</order></author></authors><documents><document><filename>0036275-26012018123123.pdf</filename><originalFilename>Frontiers.fimmu-08-01516.pdf</originalFilename><uploaded>2018-01-26T12:31:23.9430000</uploaded><type>Output</type><contentLength>3555791</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><embargoDate>2018-01-26T00:00:00.0000000</embargoDate><documentNotes>Copyright: © 2017 Jones, Cronin, Dolton, Panetti, Schauenburg, Galloway, Sewell, Cole, Thornton and Francis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling	2020-07-14T12:05:10.7627766 v2 36275 2017-10-26 Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation 0fce0f7ddbdbfeb968f4e2f1e3f86744 0000-0003-4846-5117 Nick Jones Nick Jones true false 9cfd17551c0d1f7438895121e4fbb6e8 0000-0002-0590-9462 James Cronin James Cronin true false c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false a726d297bbed7e5cd4c320f8f9dbf4d7 Nigel Francis Nigel Francis true false 2017-10-26 BMS Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell receptor (TCR) and peptides presented by human leukocyte antigens (pHLA). The role of TCR-pHLA interactions in modulating T-cell metabolism is unknown. Here for the first time we explore the relative contributions of the main metabolic pathways to functional responses in human CD4+ and CD8+ T-cells. Increased expression of hexokinase II accompanied by higher basal glycolysis is demonstrated in CD4+ T-cells; cytokine production in CD8+ T-cells is more reliant on oxidative phosphorylation. Using antigen-specific CD4+ and CD8+ T cell clones and altered peptide ligands we demonstrate that binding affinity tunes the underlying metabolic shift. Overall this study provides important new insight into how metabolic pathways are controlled during antigen-specific activation of human T-cells. Journal Article Frontiers in Immunology 8 1516 1664-3224 T-cell, immunometabolism, metabolism, TCR, glycolysis, GLUT1 31 12 2017 2017-12-31 10.3389/fimmu.2017.01516 The Supplementary Material for this article can be found online at http://www.frontiersin.org/article/10.3389/fimmu.2017.01516/full#supplementary-material COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Swansea University Medical School 2020-07-14T12:05:10.7627766 2017-10-26T11:20:59.8880360 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Nick Jones 0000-0003-4846-5117 1 James Cronin 0000-0002-0590-9462 2 Garry Dolton 3 Silvia Panetti 4 Andrea J. Schauenburg 5 Sarah A. E. Galloway 6 Andrew K. Sewell 7 David K. Cole 8 Cathy Thornton 0000-0002-5153-573X 9 Nigel Francis 10 0036275-26012018123123.pdf Frontiers.fimmu-08-01516.pdf 2018-01-26T12:31:23.9430000 Output 3555791 application/pdf Version of Record true 2018-01-26T00:00:00.0000000 Copyright: © 2017 Jones, Cronin, Dolton, Panetti, Schauenburg, Galloway, Sewell, Cole, Thornton and Francis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. true eng
title	Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation
spellingShingle	Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation Nick Jones James Cronin Cathy Thornton Nigel Francis
title_short	Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation
title_full	Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation
title_fullStr	Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation
title_full_unstemmed	Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation
title_sort	Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation
author_id_str_mv	0fce0f7ddbdbfeb968f4e2f1e3f86744 9cfd17551c0d1f7438895121e4fbb6e8 c71a7a4be7361094d046d312202bce0c a726d297bbed7e5cd4c320f8f9dbf4d7
author_id_fullname_str_mv	0fce0f7ddbdbfeb968f4e2f1e3f86744_*_Nick Jones 9cfd17551c0d1f7438895121e4fbb6e8__James Cronin c71a7a4be7361094d046d312202bce0c__Cathy Thornton a726d297bbed7e5cd4c320f8f9dbf4d7_*_Nigel Francis
author	Nick Jones James Cronin Cathy Thornton Nigel Francis
author2	Nick Jones James Cronin Garry Dolton Silvia Panetti Andrea J. Schauenburg Sarah A. E. Galloway Andrew K. Sewell David K. Cole Cathy Thornton Nigel Francis
format	Journal article
container_title	Frontiers in Immunology
container_volume	8
container_issue	1516
publishDate	2017
institution	Swansea University
issn	1664-3224
doi_str_mv	10.3389/fimmu.2017.01516
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
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hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description	Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell receptor (TCR) and peptides presented by human leukocyte antigens (pHLA). The role of TCR-pHLA interactions in modulating T-cell metabolism is unknown. Here for the first time we explore the relative contributions of the main metabolic pathways to functional responses in human CD4+ and CD8+ T-cells. Increased expression of hexokinase II accompanied by higher basal glycolysis is demonstrated in CD4+ T-cells; cytokine production in CD8+ T-cells is more reliant on oxidative phosphorylation. Using antigen-specific CD4+ and CD8+ T cell clones and altered peptide ligands we demonstrate that binding affinity tunes the underlying metabolic shift. Overall this study provides important new insight into how metabolic pathways are controlled during antigen-specific activation of human T-cells.
published_date	2017-12-31T03:45:18Z
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Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation

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