1. Translation is actively regulated during effector CD8+ T cell differentiation
- Author
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Araki, Koichi, Morita, Masahiro, Bederman, Annelise G., Konieczny, Bogumila T, Kissick, Haydn T., Sonenberg, Nahum, and Ahmed, Rafi
- Subjects
Ribosomal Proteins ,Reverse Transcriptase Polymerase Chain Reaction ,TOR Serine-Threonine Kinases ,Receptors, Antigen, T-Cell ,Cell Differentiation ,CD8-Positive T-Lymphocytes ,Flow Cytometry ,Article ,Interferon-gamma ,Mice ,Gene Expression Regulation ,Protein Biosynthesis ,Animals ,Arenaviridae Infections ,Lymphocytic choriomeningitis virus ,RNA, Messenger ,Immunologic Memory - 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 effector CD8+ T cells during acute LCMV infection of mice. Antigen-specific T cells exerted dynamic translational control of gene expression that correlated with cell proliferation and T cell antigen receptor (TCR) stimulation. Translation of mRNAs that encode translation machinery including ribosomal protein mRNAs was upregulated during the T cell expansion phase, followed by translational inhibition of these transcripts when the effector CD8+ T cells stopped dividing just prior to the contraction phase. This translational suppression was more pronounced in terminal effector cells compared to memory precursor cells, and was regulated by antigenic stimulation and mTOR signals. Our studies show that translational activity of transcripts encoding ribosomal proteins is regulated during effector CD8+ T cell differentiation and may play a role in fate decisions involved in the formation of memory cells.
- Published
- 2017