Mitochondria Are Required for Antigen-Specific T Cell Activation through Reactive Oxygen Species Signaling

Laura A. Sena, Sha Li, Amit Jairaman, Murali Prakriya, Teresa Ezponda, David A. Hildeman, Chyung Ru Wang, Paul T. Schumacker, Jonathan D. Licht, Harris Perlman, Paul J. Bryce, Navdeep S. Chandel*

*Corresponding author for this work

Research output: Contribution to journalArticle

442 Scopus citations

Abstract

It is widely appreciated that T cells increase glycolytic flux during activation, but the role of mitochondrial flux is unclear. Here, we have shown that mitochondrial metabolism in the absence of glucose metabolism is sufficient to support interleukin-2 (IL-2) induction. Furthermore, we used mice with reduced mitochondrial reactive oxygen species (mROS) production in T cells (T-Uqcrfs-/- mice) to show that mitochondria are required for T cell activation to produce mROS for activation of nuclear factor of activated T cells (NFAT) and subsequent IL-2 induction. These mice could not induce antigen-specific expansion of T cells in vivo, but Uqcrfs1-/- T cells retained the ability to proliferate in vivo under lymphopenic conditions. This suggests that Uqcrfs1-/- T cells were not lacking bioenergetically but rather lacked specific ROS-dependent signaling events needed for antigen-specific expansion. Thus, mitochondrial metabolism is a critical component of T cell activation through the production of complex III ROS.

Original languageEnglish (US)
Pages (from-to)225-236
Number of pages12
JournalImmunity
Volume38
Issue number2
DOIs
StatePublished - Feb 21 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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