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  Fever supports CD8+ effector T cell responses by promoting mitochondrial translation

O'Sullivan, D., Stanczak, M. A., Villa, M., Uhl, F. M., Corrado, M., Geltink, R. I. K., et al. (2021). Fever supports CD8+ effector T cell responses by promoting mitochondrial translation. Proceedings of the National Academy of Sciences of the United States of America, 118: e2023752118. doi:10.1073/pnas.2023752118.

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10.1073_pnas.2023752118.pdf (Publisher version), 2MB
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10.1073_pnas.2023752118.pdf
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2021
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the Author(s). Published by PNAS.

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 Creators:
O'Sullivan, David1, Author
Stanczak, Michal A1, Author
Villa, Matteo1, Author
Uhl, Franziska M2, Author
Corrado, Mauro1, Author
Geltink, Ramon I Klein1, Author
Sanin, David E1, Author
Apostolova, Petya1, Author
Rana, Nisha1, Author
Edwards-Hicks, Joy1, Author
Grzes, Katarzyna M1, Author
Kabat, Agnieszka M1, Author
Kyle, Ryan L1, Author
Fabri, Mario2, Author
Curtis, Jonathan D1, Author
Buck, Michael D1, Author
Patterson, Annette E1, Author
Regina, Annamaria2, Author
Field, Cameron S1, Author
Baixauli, Francesc1, Author
Puleston, Daniel J1, AuthorPearce, Edward Jonathen1, Author           Zeiser, Robert2, AuthorPearce, Erika Laine1, Author            more..
Affiliations:
1Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              
2External Organizations, ou_persistent22              

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Free keywords: T cell; fever; immunology; metabolism; mitochondria
 Abstract: Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8+ T cells, exposure to febrile temperature (39°C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Transcriptional profiling revealed an up-regulation of mitochondrial pathways, which was consistent with increased mass and metabolism observed in T cells exposed to 39°C. Through in vitro and in vivo models, we determined that mitochondrial translation is integral to the enhanced metabolic activity and function of CD8+ T cells exposed to febrile temperature. Transiently exposing donor lymphocytes to 39°C prior to infusion in a myeloid leukemia mouse model conferred enhanced therapeutic efficacy, raising the possibility that exposure of T cells to febrile temperatures could have clinical potential.

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Language(s): eng - English
 Dates: 2021-06-14
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1073/pnas.2023752118
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : PNAS
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 118 Sequence Number: e2023752118 Start / End Page: - Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230