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Nat Immunol. 2017 Sep;18(9):1046-1057. doi: 10.1038/ni.3795. Epub 2017 Jul 17.

Translation is actively regulated during the differentiation of CD8+ effector T cells.

Author information

1
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
2
Department of Biochemistry, McGill University, Montreal, Canada.
3
Goodman Cancer Research Centre, McGill University, Montreal, Canada.
4
Department of Urology, Emory University School of Medicine, Atlanta, Georgia, USA.

Abstract

Translation is a critical process in protein synthesis, but translational regulation in antigen-specific T cells in vivo has not been well defined. Here we have characterized the translatome of virus-specific CD8+ effector T cells (Teff cells) during acute infection of mice with lymphocytic choriomeningitis virus (LCMV). Antigen-specific T cells exerted dynamic translational control of gene expression that correlated with cell proliferation and stimulation via the T cell antigen receptor (TCR). The translation of mRNAs that encode translation machinery, including ribosomal proteins, was upregulated during the T cell clonal-expansion phase, followed by inhibition of the translation of those transcripts when the CD8+ Teff cells stopped dividing just before the contraction phase. That translational suppression was more pronounced in terminal effector cells than in memory precursor cells and was regulated by antigenic stimulation and signals from the kinase mTOR. Our studies show that translation of transcripts encoding ribosomal proteins is regulated during the differentiation of CD8+ Teff cells and might have a role in fate 'decisions' involved in the formation of memory cells.

PMID:
28714979
PMCID:
PMC5937989
DOI:
10.1038/ni.3795
[Indexed for MEDLINE]
Free PMC Article

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