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

被引:113
作者
Araki, Koichi [1 ,2 ]
Morita, Masahiro [3 ,4 ,6 ,7 ]
Bederman, Annelise G. [1 ,2 ]
Konieczny, Bogumila T. [1 ,2 ]
Kissick, Haydn T. [1 ,2 ,5 ]
Sonenberg, Nahum [3 ,4 ]
Ahmed, Rafi [1 ,2 ]
机构
[1] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[3] McGill Univ, Dept Biochem, Montreal, PQ, Canada
[4] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada
[5] Emory Univ, Sch Med, Dept Urol, Atlanta, GA USA
[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA
[7] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA
基金
美国国家卫生研究院;
关键词
IMMUNE-RESPONSE; MEMORY; MTOR; EXPRESSION; INTEGRATION; ACTIVATION; INITIATION; INFECTION; CANCER; PD-1;
D O I
10.1038/ni.3795
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1046 / +
页数:14
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