Cutting edge: Defective aerobic glycolysis defines the distinct effector function in antigen-Activated CD8+recent thymic emigrants

Cody A. Cunningham, Tessa Bergsbaken, Pamela J. Fink

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4575-4580
Number of pages6
JournalJournal of Immunology
Volume198
Issue number12
DOIs
StatePublished - Jun 15 2017

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CD8 Antigens
Glycolysis
T-Lymphocytes
Interleukin-2
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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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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Cutting edge : Defective aerobic glycolysis defines the distinct effector function in antigen-Activated CD8+recent thymic emigrants. / Cunningham, Cody A.; Bergsbaken, Tessa; Fink, Pamela J.

In: Journal of Immunology, Vol. 198, No. 12, 15.06.2017, p. 4575-4580.

Research output: Contribution to journalArticle

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