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

共 50 条

[31] Exosomes derived from hepatocellular carcinoma inhibit CD4+ and CD8+ T cell function through the PD-1/PD-L1 pathway [J].

Li, Pengpeng ;

Liu, Dianxing ;

Chen, Junmao ;

Wu, Jinghua ;

Zhang, Guozhi ;

Wang, Changyou ;

Yu, Xiangyang ;

Chen, Jianli ;

Hu, Beibei ;

Li, Changzai .

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2019, 12 (05) :5333-5340

[32] ARTC2.2/P2RX7 Signaling during Cell Isolation Distorts Function and Quantification of Tissue-Resident CD8+ T Cell and Invariant NKT Subsets [J].

da Silva, Henrique Borges ;

Wang, Haiguang ;

Qian, Lily J. ;

Hogquist, Kristin A. ;

Jameson, Stephen C. .

JOURNAL OF IMMUNOLOGY, 2019, 202 (07) :2153-2163

[33] Immunosuppressive Effects of Bryoria sp (Lichen-Forming Fungus) Extracts via Inhibition of CD8+ T-Cell Proliferation and IL-2 Production in CD4+ T Cells [J].

Hwang, Yun-Ho ;

Lee, Sung-Ju ;

Kang, Kyung-Yun ;

Hur, Jae-Seoun ;

Yee, Sung-Tae .

JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, 2017, 27 (06) :1189-1197

[34] Genetic absence of PD-L1 does not restore CD8+ T cell function during respiratory virus infection and delays virus clearance [J].

Rogers, Meredith C. ;

Lamens, Kristina D. ;

Tollefson, Sharon J. ;

Williams, John V. .

JOURNAL OF VIROLOGY, 2024, :e0079724

[35] Ectopic expression of anti-HIV-1 shRNAs protects CD8+ T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation [J].

Kamata, Masakazu ;

Kim, Patrick Y. ;

Ng, Hwee L. ;

Ringpis, Gene-Errol E. ;

Kranz, Emiko ;

Chan, Joshua ;

O'Connor, Sean ;

Yang, Otto O. ;

Chen, Irvin S. Y. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2015, 463 (03) :216-221

[36] SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy [J].

Zhang, Qi-Sheng ;

Wang, Jia-Ning ;

Yang, Tian-Ling ;

Li, Si-Yao ;

Liu, Ding-Ning ;

Shang, Hong ;

Zhang, Zi-Ning .

EBIOMEDICINE, 2025, 112

[37] CD4+ T-Helper Type 1 Cytokines and Trastuzumab Facilitate CD8+ T-cell Targeting of HER2/neu-Expressing Cancers [J].

Datta, Jashodeep ;

Xu, Shuwen ;

Rosemblit, Cinthia ;

Smith, Jenessa B. ;

Cintolo, Jessica A. ;

Powell, Daniel J., Jr. ;

Czerniecki, Brian J. .

CANCER IMMUNOLOGY RESEARCH, 2015, 3 (05) :455-463

[38] 4-1BB Signaling Activates the T Cell Factor 1 Effector/β-Catenin Pathway with Delayed Kinetics via ERK Signaling and Delayed PI3K/AKT Activation to Promote the Proliferation of CD8+ T Cells [J].

Lee, Do Y. ;

Choi, Beom K. ;

Lee, Don G. ;

Kim, Young H. ;

Kim, Chang H. ;

Lee, Seung J. ;

Kwon, Byoung S. .

PLOS ONE, 2013, 8 (07)

[39] Ezh2 Regulates Activation-Induced CD8+ T Cell Cycle Progression via Repressing Cdkn2a and Cdkn1c Expression [J].

Chen, Guobing ;

Subedi, Kalpana ;

Chakraborty, Sayantan ;

Sharov, Alexie ;

Lu, Jian ;

Kim, Jaekwan ;

Mi, Xiaofan ;

Wersto, Robert ;

Sung, Myong-Hee ;

Weng, Nan-ping .

FRONTIERS IN IMMUNOLOGY, 2018, 9

[40] Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects [J].

Joseph, Ann Mary ;

Srivastava, Ratika ;

Zabaleta, Jovanny ;

Davila, Eduardo .

CANCER IMMUNOLOGY RESEARCH, 2016, 4 (08) :708-716

← 1 2 3 4 5 →