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

David OSullivan; Michal A. Stanczak; Matteo Villa; Franziska M. Uhl; Mauro Corrado; Ramon I. Klein Geltink; David E. Sanin; Petya Apostolova; Nisha Rana; Joy Edwards-Hicks; Katarzyna M. Grzes; Agnieszka M. Kabat; Ryan L. Kyle; Mario Fabri; Jonathan D. Curtis; Michael D. Buck; Annette E. Patterson; Annamaria Regina; Cameron S. Field; Francesc Baixauli; Daniel J. Puleston; Edward J. Pearce; Robert Zeiser; Erika L. Pearce

doi:10.1073/pnas.2023752118

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

David OSullivan, Michal A. Stanczak, Matteo Villa, Franziska M. Uhl, Mauro Corrado, Ramon I. Klein Geltink, David E. Sanin, Petya Apostolova, Nisha Rana, Joy Edwards-Hicks, Katarzyna M. Grzes, Agnieszka M. Kabat, Ryan L. Kyle, Mario Fabri, Jonathan D. Curtis, Michael D. Buck, Annette E. Patterson, Annamaria Regina, Cameron S. Field, Francesc BaixauliDaniel J. Puleston, Edward J. Pearce, Robert Zeiser, Erika L. Pearce

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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.

Original language	English
Article number	e2023752118
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Issue number	25
DOIs	https://doi.org/10.1073/pnas.2023752118
State	Published - 22 Jun 2021
Externally published	Yes

Keywords

T cell
fever
immunology
metabolism
mitochondria

Access to Document

10.1073/pnas.2023752118

Cite this

OSullivan, D., Stanczak, M. A., Villa, M., Uhl, F. M., Corrado, M., Klein Geltink, R. I., Sanin, D. E., Apostolova, P., Rana, N., Edwards-Hicks, J., Grzes, K. M., Kabat, A. M., Kyle, R. L., Fabri, M., Curtis, J. D., Buck, M. D., Patterson, A. E., Regina, A., Field, C. S., ... Pearce, E. L. (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(25), Article e2023752118. https://doi.org/10.1073/pnas.2023752118

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title = "Fever supports CD8+ effector T cell responses by promoting mitochondrial translation",

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.",

keywords = "T cell, fever, immunology, metabolism, mitochondria",

author = "David OSullivan and Stanczak, {Michal A.} and Matteo Villa and Uhl, {Franziska M.} and Mauro Corrado and {Klein Geltink}, {Ramon I.} and Sanin, {David E.} and Petya Apostolova and Nisha Rana and Joy Edwards-Hicks and Grzes, {Katarzyna M.} and Kabat, {Agnieszka M.} and Kyle, {Ryan L.} and Mario Fabri and Curtis, {Jonathan D.} and Buck, {Michael D.} and Patterson, {Annette E.} and Annamaria Regina and Field, {Cameron S.} and Francesc Baixauli and Puleston, {Daniel J.} and Pearce, {Edward J.} and Robert Zeiser and Pearce, {Erika L.}",

year = "2021",

month = jun,

day = "22",

doi = "10.1073/pnas.2023752118",

language = "English",

volume = "118",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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OSullivan, D, Stanczak, MA, Villa, M, Uhl, FM, Corrado, M, Klein Geltink, RI, Sanin, DE, Apostolova, P, Rana, N, Edwards-Hicks, J, Grzes, KM, Kabat, AM, Kyle, RL, Fabri, M, Curtis, JD, Buck, MD, Patterson, AE, Regina, A, Field, CS, Baixauli, F, Puleston, DJ, Pearce, EJ, Zeiser, R & Pearce, EL 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, vol. 118, no. 25, e2023752118. https://doi.org/10.1073/pnas.2023752118

TY - JOUR

T1 - Fever supports CD8+ effector T cell responses by promoting mitochondrial translation

AU - OSullivan, David

AU - Stanczak, Michal A.

AU - Villa, Matteo

AU - Uhl, Franziska M.

AU - Corrado, Mauro

AU - Klein Geltink, Ramon I.

AU - Sanin, David E.

AU - Apostolova, Petya

AU - Rana, Nisha

AU - Edwards-Hicks, Joy

AU - Grzes, Katarzyna M.

AU - Kabat, Agnieszka M.

AU - Kyle, Ryan L.

AU - Fabri, Mario

AU - Curtis, Jonathan D.

AU - Buck, Michael D.

AU - Patterson, Annette E.

AU - Regina, Annamaria

AU - Field, Cameron S.

AU - Baixauli, Francesc

AU - Puleston, Daniel J.

AU - Pearce, Edward J.

AU - Zeiser, Robert

AU - Pearce, Erika L.

PY - 2021/6/22

Y1 - 2021/6/22

N2 - 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.

AB - 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.

KW - T cell

KW - fever

KW - immunology

KW - metabolism

KW - mitochondria

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U2 - 10.1073/pnas.2023752118

DO - 10.1073/pnas.2023752118

M3 - Article

C2 - 34161266

AN - SCOPUS:85107963011

SN - 0027-8424

VL - 118

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 25

M1 - e2023752118