Cutting Edge: Defective Aerobic Glycolysis Defines the Distinct Effector Function in Antigen-Activated CD8+ Recent Thymic Emigrants

The Journal of Immunology : Official Journal of the American Association of Immunologists
Cody A CunninghamPamela J Fink

Abstract

Recent thymic emigrants (RTEs) are the youngest peripheral T cells that have completed thymic selection and egress to the lymphoid periphery. RTEs are functionally distinct from their more mature but still naive T cell counterparts, because they exhibit dampened proliferation and reduced cytokine production upon activation. In this article, we show that, compared with more mature but still naive T cells, RTEs are impaired in their ability to perform aerobic glycolysis following activation. Impaired metabolism underlies the reduced IFN-γ production observed in activated RTEs. This failure to undergo Ag-induced aerobic glycolysis is caused by reduced mTORC1 activity and diminished Myc induction in RTEs. Critically, exogenous IL-2 restores Myc expression in RTEs, driving aerobic glycolysis and IFN-γ production to the level of mature T cells. These results reveal a previously unknown metabolic component to postthymic T cell maturation.

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Citations

Mar 10, 2018·Nature Reviews. Immunology·Theo van den BroekFemke van Wijk
Dec 31, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shusong ZhangQing Ge
Aug 3, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cody A CunninghamPamela J Fink
May 28, 2019·Immunology and Cell Biology·David O'Sullivan
Jul 2, 2019·Journal of Leukocyte Biology·Adam J FikeAlison J Carey
Mar 10, 2020·Immunological Reviews·Haiping WangPing-Chih Ho
Apr 21, 2018·Annual Review of Immunology·Ramon I Klein GeltinkErika L Pearce
Dec 20, 2017·Current Opinion in Immunology·Cody A CunninghamPamela J Fink
Apr 28, 2021·Annual Review of Immunology·Elizabeth M SteinertNavdeep S Chandel
Oct 15, 2021·European Journal of Immunology·Clarissa Braun, Thomas Weichhart

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