Scientific Reports (Dec 2020)

Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species

  • Anouk Lepez,
  • Tiphène Pirnay,
  • Sébastien Denanglaire,
  • David Perez-Morga,
  • Marjorie Vermeersch,
  • Oberdan Leo,
  • Fabienne Andris

DOI
https://doi.org/10.1038/s41598-020-78715-2
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 14

Abstract

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Abstract The AMP-activated kinase (AMPK) is a major energy sensor metabolic enzyme that is activated early during T cell immune responses but its role in the generation of effector T cells is still controversial. Using both in vitro and in vivo models of T cell proliferation, we show herein that AMPK is dispensable for early TCR signaling and short-term proliferation but required for sustained long-term T cell proliferation and effector/memory T cell survival. In particular, AMPK promoted accumulation of effector/memory T cells in competitive homeostatic proliferation settings. Transplantation of AMPK-deficient hematopoïetic cells into allogeneic host recipients led to a reduced graft-versus-host disease, further bolstering a role for AMPK in the expansion and pathogenicity of effector T cells. Mechanistically, AMPK expression enhances the mitochondrial membrane potential of T cells, limits reactive oxygen species (ROS) production, and resolves ROS-mediated toxicity. Moreover, dampening ROS production alleviates the proliferative defect of AMPK-deficient T cells, therefore indicating a role for an AMPK-mediated ROS control of T cell fitness.