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

• Type of Material: Article
• Authors: Koichi Araki, Emory University; Masahiro Morita, McGill University; Annelise G. Bederman, Emory University; Bogumila T. Konieczny, Emory University; Haydn Thomas Kissick, Emory University; Nahum Sonenberg, McGill University; Rafi Ahmed, Emory University
• Language: English
• Date: 2017-09-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/ni.3795
• Title of Journal or Parent Work: Nature Immunology
• ISSN: 1529-2908
• Volume: 18
• Issue: 9
• Start Page: 1046
• End Page: 1057
• Grant/Funding Information: This study is supported by grants from NIH R01 AI030048 to R.A. and the Mérieux Foundation to R.A.
• Keywords: CANCER; VIRUS-INFECTION; Science & Technology; MTOR; Life Sciences & Biomedicine; IMMUNE-RESPONSE; Cellular immunity; MESSENGER-RNA TRANSLATION; CHRONIC VIRAL-INFECTION; EXPRESSION; MEMORY; INTEGRATION; INFLAMMATION; Infectious diseases; Immunology
• Research Categories: Health Sciences, Immunology; Biology, Microbiology; Chemistry, Biochemistry

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 (T eff 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 + T eff 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 + T eff cells and might have a role in fate 'decisions' involved in the formation of memory cells.