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

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 rec...

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Autores principales: Jones, Nicholas, Cronin, James G., Dolton, Garry, Panetti, Silvia, Schauenburg, Andrea J., Galloway, Sarah A. E., Sewell, Andrew K., Cole, David K., Thornton, Catherine A., Francis, Nigel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684100/
https://www.ncbi.nlm.nih.gov/pubmed/29170670
http://dx.doi.org/10.3389/fimmu.2017.01516
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author Jones, Nicholas
Cronin, James G.
Dolton, Garry
Panetti, Silvia
Schauenburg, Andrea J.
Galloway, Sarah A. E.
Sewell, Andrew K.
Cole, David K.
Thornton, Catherine A.
Francis, Nigel J.
author_facet Jones, Nicholas
Cronin, James G.
Dolton, Garry
Panetti, Silvia
Schauenburg, Andrea J.
Galloway, Sarah A. E.
Sewell, Andrew K.
Cole, David K.
Thornton, Catherine A.
Francis, Nigel J.
author_sort Jones, Nicholas
collection PubMed
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.
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spelling pubmed-56841002017-11-23 Metabolic Adaptation of Human CD4(+) and CD8(+) T-Cells to T-Cell Receptor-Mediated Stimulation Jones, Nicholas Cronin, James G. Dolton, Garry Panetti, Silvia Schauenburg, Andrea J. Galloway, Sarah A. E. Sewell, Andrew K. Cole, David K. Thornton, Catherine A. Francis, Nigel J. Front Immunol Immunology 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. Frontiers Media S.A. 2017-11-09 /pmc/articles/PMC5684100/ /pubmed/29170670 http://dx.doi.org/10.3389/fimmu.2017.01516 Text en Copyright © 2017 Jones, Cronin, Dolton, Panetti, Schauenburg, Galloway, Sewell, Cole, Thornton and Francis. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Immunology
Jones, Nicholas
Cronin, James G.
Dolton, Garry
Panetti, Silvia
Schauenburg, Andrea J.
Galloway, Sarah A. E.
Sewell, Andrew K.
Cole, David K.
Thornton, Catherine A.
Francis, Nigel J.
Metabolic Adaptation of Human CD4(+) and CD8(+) T-Cells to T-Cell Receptor-Mediated Stimulation
title 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_short 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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684100/
https://www.ncbi.nlm.nih.gov/pubmed/29170670
http://dx.doi.org/10.3389/fimmu.2017.01516
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