Translational Control by 4E-BP1/2 Suppressor Proteins Regulates Mitochondrial Biosynthesis and Function during CD8+ T Cell Proliferation

被引：1

作者：

Dimitriou, Ioannis D. ^{[1
]}

Meiri, David ^{[2
]}

Jitkova, Yulia ^{[1
]}

Elford, Alisha R. ^{[1
]}

Koritzinsky, Marianne ^{[1
]}

Schimmer, Aaron D. ^{[1
]}

Ohashi, Pamela S. ^{[1
]}

Sonenberg, Nahum ^{[3
,4
]}

Rottapel, Robert ^{[1
,5
,6
,7
]}

机构：

[1] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[2] Technion Israel Inst Technol, Fac Biol, Haifa, Israel

[3] McGill Univ, Dept Biochem, Montreal, PQ, Canada

[4] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Montreal, PQ, Canada

[5] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[6] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[7] Univ Toronto, Dept Med, Toronto, ON, Canada

来源：

JOURNAL OF IMMUNOLOGY | 2022年 / 208卷 / 12期

基金：

加拿大健康研究院;

关键词：

MOLECULAR-MECHANISMS; MEMORY; EIF4E; ACTIVATION; METABOLISM; COMPLEX; MTORC1; INHIBITION; EXPRESSION; RAPAMYCIN;

D O I：

10.4049/jimmunol.2101090

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

CD8(+) T cell proliferation and differentiation into effector and memory states are high-energy processes associated with changes in cellular metabolism. CD28-mediated costimulation of T cells activates the PI3K/AKT/mammalian target of rapamycin signaling pathway and induces eukaryotic translation initiation factor 4E-dependent translation through the derepression by 4E-BP1 and 4E-BP2. In this study, we demonstrate that 4E-BP1/2 proteins are required for optimum proliferation of mouse CD8(+) T cells and the development of an antiviral effector function. We show that translation of genes encoding mitochondrial biogenesis is impaired in T cells derived from 4E-BP1/2-deficient mice. Our findings demonstrate an unanticipated role for 4E-BPs in regulating a metabolic program that is required for cell growth and biosynthesis during the early stages of CD8(+) T cell expansion.

引用

页码：2702 / 2712

页数：12

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[41] Mice deficient in stem cell antigen-1 (Sca1, Ly-6A/E) develop normal primary and memory CD4+ and CD8+ T-cell responses to virus infection [J].

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Johnson, Randall C. ;

Kwon, Douglas S. ;

Addo, Marylyn M. ;

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Hecht, Frederick M. ;

Sekaly, Rafick-Pierre ;

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[46] Co-Stimulation through 4-1BB/CD137 Improves the Expansion and Function of CD8+ Melanoma Tumor-Infiltrating Lymphocytes for Adoptive T-Cell Therapy [J].

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Sarnaik, Amod ;

Pilon-Thomas, Shari ;

Weber, Jeffrey ;

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[47] Cutting Edge: Activation-Induced Iron Flux Controls CD4 T Cell Proliferation by Promoting Proper IL-2R Signaling and Mitochondrial Function [J].

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