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

• 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
• Journal Title: Nature Immunology
• Volume: Volume 18, Number 9
• Publisher: Nature Publishing Group | 2017-09-01, Pages 1046-1057
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/ni.3795
• Subjects: Health Sciences, Immunology; Biology, Microbiology; Chemistry, Biochemistry
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; MESSENGER-RNA TRANSLATION; CHRONIC VIRAL-INFECTION; IMMUNE-RESPONSE; VIRUS-INFECTION; MEMORY; MTOR; CANCER; EXPRESSION; INFLAMMATION; INTEGRATION; Cellular immunity; Infectious diseases

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.