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


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.

SUBMITTER: Sena LA 

PROVIDER: S-EPMC3582741 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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

Sena Laura A LA   Li Sha S   Jairaman Amit A   Prakriya Murali M   Ezponda Teresa T   Hildeman David A DA   Wang Chyung-Ru CR   Schumacker Paul T PT   Licht Jonathan D JD   Perlman Harris H   Bryce Paul J PJ   Chandel Navdeep S NS  

Immunity 20130215 2


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 nucle  ...[more]

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