Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling

Immunity. 2013 Feb 21;38(2):225-36. doi: 10.1016/j.immuni.2012.10.020. Epub 2013 Feb 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Electron Transport Complex III / metabolism
  • Female
  • Gene Expression
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Iron-Sulfur Proteins / deficiency
  • Iron-Sulfur Proteins / genetics
  • Lymphocyte Activation
  • Lymphopenia / immunology
  • Lymphopenia / metabolism
  • Mice
  • Mice, Knockout
  • Mitochondria / genetics
  • Mitochondria / immunology
  • Mitochondria / metabolism*
  • NFATC Transcription Factors / genetics*
  • NFATC Transcription Factors / immunology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology


  • Homeodomain Proteins
  • Interleukin-2
  • Iron-Sulfur Proteins
  • NFATC Transcription Factors
  • Reactive Oxygen Species
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • RAG-1 protein
  • Electron Transport Complex III