A central role for Notch in effector CD8+ T cell differentiation

被引：98

作者：

Backer, Ronald A. ^{[1
,2
]}

Helbig, Christina ^{[1
,2
]}

Gentek, Rebecca ^{[1
]}

Kent, Andrew ^{[3
,4
]}

Laidlaw, Brian J. ^{[5
,6
]}

Dominguez, Claudia X. ^{[5
,6
]}

de Souza, Yevan S. ^{[1
]}

van Trierum, Stella E. ^{[7
,8
]}

van Beek, Ruud ^{[7
,8
]}

Rimmelzwaan, Guus F. ^{[7
,8
]}

ten Brinke, Anja ^{[9
]}

Willemsen, A. Marcel ^{[10
]}

van Kampen, Antoine H. C. ^{[10
]}

Kaech, Susan M. ^{[5
,6
]}

Blander, J. Magarian ^{[3
,4
]}

van Gisbergen, Klaas ^{[2
]}

Amsen, Derk ^{[1
,2
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands

[2] Sanquin Res & Landsteiner Lab, Dept Hematopoiesis, Amsterdam, Netherlands

[3] Icahn Sch Med Mt Sinai, Inst Immunol, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Med, New York, NY 10029 USA

[5] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA

[6] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA

[7] Erasmus MC, Dept Virosci, Rotterdam, Netherlands

[8] Viroclin Biosci BV, Rotterdam, Netherlands

[9] Sanquin Res & Landsteiner Lab, Dept Immunopathol, Amsterdam, Netherlands

[10] Univ Amsterdam, Acad Med Ctr, Bioinformat Lab, NL-1105 AZ Amsterdam, Netherlands

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 12期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

TRANSCRIPTION FACTOR; VIRAL-INFECTION; CD25; EXPRESSION; DENDRITIC CELLS; VIRUS-INFECTION; IN-VIVO; MEMORY; PATHWAY; METABOLISM; RESPONSES;

D O I：

10.1038/ni.3027

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We found that the signaling receptor Notch controls this 'choice'. Notch promoted the differentiation of immediately protective TECs and was correspondingly required for the clearance of acute infection with influenza virus. Notch activated a major portion of the TEC-specific gene-expression program and suppressed the MPC-specific program. Expression of Notch was induced on naive CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via pathways dependent on the metabolic checkpoint kinase mTOR and the transcription factor T-bet. These pathways were subsequently amplified downstream of Notch, creating a positive feedback loop. Notch thus functions as a central hub where information from different sources converges to match effector T cell differentiation to the demands of an infection.

引用

页码：1143 / 1151

页数：9

共 53 条

[1] Notch signaling augments T cell responsiveness by enhancing CD25 expression
Adler, SH
Chiffoleau, E
Xu, LW
Dalton, NM
Burg, JM
Wells, AD
Wolfe, MS
Turka, LA
Pear, WS
[J]. JOURNAL OF IMMUNOLOGY, 2003, 171 (06) : 2896 - 2903
[2] Recognition of pathogen-associated molecular patterns by TLR family
Akira, S
Hemmi, H
[J]. IMMUNOLOGY LETTERS, 2003, 85 (02) : 85 - 95
[3] Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells
Amsen, D
Blander, JM
Lee, GR
Tanigaki, K
Honjo, T
Flavell, RA
[J]. CELL, 2004, 117 (04) : 515 - 526
[4] Direct regulation of Gata3 expression determines the T helper differentiation potential of notch
Amsen, Derk
Antov, Andrey
Jankovic, Dragana
Sher, Alan
Radtke, Freddy
Souabni, Abdallah
Busslinger, Meinrad
McCright, Brent
Gridley, Thomas
Flavell, Richard A.
[J]. IMMUNITY, 2007, 27 (01) : 89 - 99
[5] mTOR regulates memory CD8 T-cell differentiation
Araki, Koichi
Turner, Alexandra P.
Shaffer, Virginia Oliva
Gangappa, Shivaprakash
Keller, Susanne A.
Bachmann, Martin F.
Larsen, Christian P.
Ahmed, Rafi
[J]. NATURE, 2009, 460 (7251) : 108 - U124
[6] CD8+ T cell contraction is controlled by early inflammation
Badovinac, VP
Porter, BB
Harty, JT
[J]. NATURE IMMUNOLOGY, 2004, 5 (08) : 809 - 817
[7] Notch Simultaneously Orchestrates Multiple Helper T Cell Programs Independently of Cytokine Signals
Bailis, Will
Yashiro-Ohtani, Yumi
Fang, Terry C.
Hatton, Robin D.
Weaver, Casey T.
Artis, David
Pear, Warren S.
[J]. IMMUNITY, 2013, 39 (01) : 148 - 159
[8] A previously unrecognized H-2Db-restricted peptide prominent in the primary influenza A virus-specific CD8+ T-cell response is much less apparent following secondary challenge
Belz, GT
Xie, WD
Altman, JD
Doherty, PC
[J]. JOURNAL OF VIROLOGY, 2000, 74 (08) : 3486 - 3493
[9] Regulating the adaptive immune response to respiratory virus infection
Braciale, Thomas J.
Sun, Jie
Kim, Taeg S.
[J]. NATURE REVIEWS IMMUNOLOGY, 2012, 12 (04) : 295 - 305
[10] Notch signalling: a simple pathway becomes complex
Bray, Sarah J.
[J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2006, 7 (09) : 678 - 689

← 1 2 3 4 5 6 →