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Nat Immunol. 2016 Jun;17(6):704-11. doi: 10.1038/ni.3438. Epub 2016 Apr 11.

Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation.

Author information

1
Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2
Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abstract

The asymmetric partitioning of fate-determining proteins has been shown to contribute to the generation of CD8(+) effector and memory T cell precursors. Here we demonstrate the asymmetric partitioning of mTORC1 activity after the activation of naive CD8(+) T cells. This results in the generation of two daughter T cells, one of which shows increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell has relatively low mTORC1 activity and increased lipid metabolism, expresses increased amounts of anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between T cell antigen receptor (TCR)-induced asymmetric expression of amino acid transporters and RagC-mediated translocation of mTOR to the lysosomes. Overall, our data provide important insight into how mTORC1-mediated metabolic reprogramming affects the fate decisions of T cells.

PMID:
27064374
PMCID:
PMC4873361
DOI:
10.1038/ni.3438
[Indexed for MEDLINE]
Free PMC Article

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