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Early changes in the metabolic profile of activated CD8(+) T cells

BACKGROUND: Antigenic stimulation of the T cell receptor (TCR) initiates a change from a resting state into an activated one, which ultimately results in proliferation and the acquisition of effector functions. To accomplish this task, T cells require dramatic changes in metabolism. Therefore, we in...

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Autores principales: Cammann, Clemens, Rath, Alexander, Reichl, Udo, Lingel, Holger, Brunner-Weinzierl, Monika, Simeoni, Luca, Schraven, Burkhart, Lindquist, Jonathan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937576/
https://www.ncbi.nlm.nih.gov/pubmed/27387758
http://dx.doi.org/10.1186/s12860-016-0104-x
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author Cammann, Clemens
Rath, Alexander
Reichl, Udo
Lingel, Holger
Brunner-Weinzierl, Monika
Simeoni, Luca
Schraven, Burkhart
Lindquist, Jonathan A.
author_facet Cammann, Clemens
Rath, Alexander
Reichl, Udo
Lingel, Holger
Brunner-Weinzierl, Monika
Simeoni, Luca
Schraven, Burkhart
Lindquist, Jonathan A.
author_sort Cammann, Clemens
collection PubMed
description BACKGROUND: Antigenic stimulation of the T cell receptor (TCR) initiates a change from a resting state into an activated one, which ultimately results in proliferation and the acquisition of effector functions. To accomplish this task, T cells require dramatic changes in metabolism. Therefore, we investigated changes of metabolic intermediates indicating for crucial metabolic pathways reflecting the status of T cells. Moreover we analyzed possible regulatory molecules required for the initiation of the metabolic changes. RESULTS: We found that proliferation inducing conditions result in an increase in key glycolytic metabolites, whereas the citric acid cycle remains unaffected. The upregulation of glycolysis led to a strong lactate production, which depends upon AKT/PKB, but not mTOR. The observed upregulation of lactate dehydrogenase results in increased lactate production, which we found to be dependent on IL-2 and to be required for proliferation. Additionally we observed upregulation of Glucose-transporter 1 (GLUT1) and glucose uptake upon stimulation, which were surprisingly not influenced by AKT inhibition. CONCLUSIONS: Our findings suggest that AKT plays a central role in upregulating glycolysis via induction of lactate dehydrogenase expression, but has no impact on glucose uptake of T cells. Furthermore, under apoptosis inducing conditions, T cells are not able to upregulate glycolysis and induce lactate production. In addition maintaining high glycolytic rates strongly depends on IL-2 production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-016-0104-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-49375762016-07-09 Early changes in the metabolic profile of activated CD8(+) T cells Cammann, Clemens Rath, Alexander Reichl, Udo Lingel, Holger Brunner-Weinzierl, Monika Simeoni, Luca Schraven, Burkhart Lindquist, Jonathan A. BMC Cell Biol Research Article BACKGROUND: Antigenic stimulation of the T cell receptor (TCR) initiates a change from a resting state into an activated one, which ultimately results in proliferation and the acquisition of effector functions. To accomplish this task, T cells require dramatic changes in metabolism. Therefore, we investigated changes of metabolic intermediates indicating for crucial metabolic pathways reflecting the status of T cells. Moreover we analyzed possible regulatory molecules required for the initiation of the metabolic changes. RESULTS: We found that proliferation inducing conditions result in an increase in key glycolytic metabolites, whereas the citric acid cycle remains unaffected. The upregulation of glycolysis led to a strong lactate production, which depends upon AKT/PKB, but not mTOR. The observed upregulation of lactate dehydrogenase results in increased lactate production, which we found to be dependent on IL-2 and to be required for proliferation. Additionally we observed upregulation of Glucose-transporter 1 (GLUT1) and glucose uptake upon stimulation, which were surprisingly not influenced by AKT inhibition. CONCLUSIONS: Our findings suggest that AKT plays a central role in upregulating glycolysis via induction of lactate dehydrogenase expression, but has no impact on glucose uptake of T cells. Furthermore, under apoptosis inducing conditions, T cells are not able to upregulate glycolysis and induce lactate production. In addition maintaining high glycolytic rates strongly depends on IL-2 production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-016-0104-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-07 /pmc/articles/PMC4937576/ /pubmed/27387758 http://dx.doi.org/10.1186/s12860-016-0104-x Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Cammann, Clemens
Rath, Alexander
Reichl, Udo
Lingel, Holger
Brunner-Weinzierl, Monika
Simeoni, Luca
Schraven, Burkhart
Lindquist, Jonathan A.
Early changes in the metabolic profile of activated CD8(+) T cells
title Early changes in the metabolic profile of activated CD8(+) T cells
title_full Early changes in the metabolic profile of activated CD8(+) T cells
title_fullStr Early changes in the metabolic profile of activated CD8(+) T cells
title_full_unstemmed Early changes in the metabolic profile of activated CD8(+) T cells
title_short Early changes in the metabolic profile of activated CD8(+) T cells
title_sort early changes in the metabolic profile of activated cd8(+) t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937576/
https://www.ncbi.nlm.nih.gov/pubmed/27387758
http://dx.doi.org/10.1186/s12860-016-0104-x
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