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

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

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.

MeSH terms

  • Animals
  • Arenaviridae Infections / genetics
  • Arenaviridae Infections / immunology*
  • Arenaviridae Infections / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Flow Cytometry
  • Gene Expression Regulation
  • Immunologic Memory / immunology
  • Interferon-gamma / immunology
  • Lymphocytic choriomeningitis virus
  • Mice
  • Protein Biosynthesis / genetics
  • Protein Biosynthesis / immunology*
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • TOR Serine-Threonine Kinases / immunology

Substances

  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Ribosomal Proteins
  • Interferon-gamma
  • TOR Serine-Threonine Kinases