Mitochondrial Priming by CD28

Geltink, Ramon I. Klein; O’Sullivan, David; Corrado, Mauro; Bremser, Anna; Buck, Michael D.; Buescher, Joerg M.; Firat, Elke; Zhu, Xuekai; Niedermann, Gabriele; Caputa, George; Kelly, Beth; Warthorst, Ursula; Rensing-Ehl, Anne; Kyle, Ryan L.; Vandersarren, Lana; Curtis, Jonathan D.; Patterson, Annette E.; Lawless, Simon; Grzes, Katarzyna; Qiu, Jing; Sanin, David E.; Kretz, Oliver; Huber, Tobias B.; Janssens, Sophie; Lambrecht, Bart N.; Rambold, Angelika; Pearce, Edward J.; Pearce, Erika L.

doi:10.1016/j.immuni.2017.03.022

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Mitochondrial Priming by CD28

MPS-Authors

Geltink, Ramon I. Klein
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

O’Sullivan, David
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Corrado, Mauro
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Bremser, Anna
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Buck, Michael D.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Buescher, Joerg M.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Caputa, George
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kelly, Beth
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kyle, Ryan L.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Curtis, Jonathan D.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Patterson, Annette E.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Lawless, Simon
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Grzes, Katarzyna
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Qiu, Jing
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sanin, David E.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Rambold, Angelika
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201435

Pearce, Edward J.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201431

Pearce, Erika L.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S0092867417309431?via%3Dihub
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Citation

Geltink, R. I. K., O’Sullivan, D., Corrado, M., Bremser, A., Buck, M. D., Buescher, J. M., et al. (2017). Mitochondrial Priming by CD28. Cell, 171, 385-397. doi:10.1016/j.immuni.2017.03.022.

Cite as: http://hdl.handle.net/11858/00-001M-0000-002E-8575-1

Abstract

T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand. Early CD28-dependent mitochondrial engagement is needed for T cells to remodel cristae, develop SRC, and rapidly produce cytokines upon restimulation—cardinal features of protective memory T cells. Our data show that initial CD28 signals during T cell activation prime mitochondria with latent metabolic capacity that is essential for future T cell responses.