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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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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. |
format | Online Article Text |
id | pubmed-4937576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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