Infectious tolerance via the consumption of essential amino acids and mTOR signaling

被引：274

作者：

Cobbold, Stephen P. ^{[1
]}

Adams, Elizabeth ^{[1
]}

Farquhar, Claire A. ^{[1
]}

Nolan, Kathleen F. ^{[1
]}

Howie, Duncan ^{[1
]}

Lui, Kathy O. ^{[1
]}

Fairchild, Paul J. ^{[1
]}

Mellor, Andrew L. ^{[2
]}

Ron, David ^{[3
]}

Waldmann, Herman ^{[1
]}

机构：

[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[2] Med Coll Georgia, Dept Med, Immunotherapy Ctr, Augusta, GA 30912 USA

[3] New York Sch Med, Skirball Inst Biomol Med, Dept Med, New York, NY 10016 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 29期

基金：

美国国家卫生研究院;

关键词：

amino acid catabolism; foxp3; mTOR inhibitor; regulatory T cells; rapamycin; REGULATORY T-CELLS; DENDRITIC CELLS; INDOLEAMINE 2,3-DIOXYGENASE; FOXP3; EXPRESSION; GCN2; KINASE; INDUCTION; REJECTION; SUBSETS; IDO; TRANSLATION;

D O I：

10.1073/pnas.0903919106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Infectious tolerance describes the process of CD4(+) regulatory T cells (Tregs) converting naive T cells to become additional Tregs. We show that antigen-specific Tregs induce, within skin grafts and dendritic cells, the expression of enzymes that consume at least 5 different essential amino acids (EAAs). T cells fail to proliferate in response to antigen when any 1, or more, of these EAAs are limiting, which is associated with a reduced mammalian target of rapamycin (mTOR) signaling. Inhibition of the mTOR pathway by limiting EAAs, or by specific inhibitors, induces the Treg-specific transcription factor forkhead box P3, which depends on both T cell receptor activation and synergy with TGF-beta.

引用

页码：12055 / 12060

页数：6

共 43 条

[1]

Regulation of immune responses by L- arginine metabolism [J].

Bronte, V ;

Zanovello, P .

NATURE REVIEWS IMMUNOLOGY, 2005, 5 (08) :641-654

[2]

FOXP3 expression in human kidney transplant biopsies is associated with rejection and time post transplant but not with favorable outcomes [J].

Bunnag, S. ;

Allanach, K. ;

Jhangri, G. S. ;

Sis, B. ;

Einecke, G. ;

Mengel, M. ;

Mueller, T. F. ;

Halloran, P. F. .

AMERICAN JOURNAL OF TRANSPLANTATION, 2008, 8 (07) :1423-1433

[3]

Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants [J].

Cobbold, SP ;

Castejon, R ;

Adams, E ;

Zelenika, D ;

Graca, L ;

Humm, S ;

Waldmann, H .

JOURNAL OF IMMUNOLOGY, 2004, 172 (10) :6003-6010

[4]

Regulatory T cells and dendritic cells in transplantation tolerance: molecular markers and mechanisms [J].

Cobbold, SP ;

Nolan, KF ;

Graca, L ;

Castejon, R ;

Le Moine, A ;

Frewin, M ;

Humm, S ;

Adams, E ;

Thompson, S ;

Zelenika, D ;

Paterson, A ;

Yates, S ;

Fairchild, PJ ;

Waldmann, H .

IMMUNOLOGICAL REVIEWS, 2003, 196 (01) :109-124

[5]

Immune privilege induced by regulatory T cells in transplantation tolerance [J].

Cobbold, Stephen P. ;

Adams, Elizabeth ;

Graca, Luis ;

Daley, Stephen ;

Yates, Stephen ;

Paterson, Alison ;

Robertson, Nathan J. ;

Nolan, Kathleen F. ;

Fairchild, Paul J. ;

Waldmann, Herman .

IMMUNOLOGICAL REVIEWS, 2006, 213 :239-255

[6]

A key role for TGF-β signaling to T cells in the long-term acceptance of Allografts [J].

Daley, Stephen R. ;

Ma, Jianbo ;

Adams, Elizabeth ;

Cobbold, Stephen P. ;

Waldmann, Herman .

JOURNAL OF IMMUNOLOGY, 2007, 179 (06) :3648-3654

[7]

Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression [J].

Deaglio, Silvia ;

Dwyer, Karen M. ;

Gao, Wenda ;

Friedman, David ;

Usheva, Anny ;

Erat, Anna ;

Chen, Jiang-Fan ;

Enjyoji, Keiichii ;

Linden, Joel ;

Oukka, Mohamed ;

Kuchroo, Vijay K. ;

Strom, Terry B. ;

Robson, Simon C. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (06) :1257-1265

[8]

Intragraft FOXP3 mRNA expression reflects antidonor immune reactivity in cardiac allograft patients [J].

Dijke, I. Esme ;

Velthuis, Jurien H. L. ;

Caliskan, Kadir ;

Korevaar, Sander S. ;

Maat, Alex P. W. M. ;

Zondervan, Pieter E. ;

Balk, Aggie H. M. M. ;

Weimar, Willem ;

Baan, Carla C. .

TRANSPLANTATION, 2007, 83 (11) :1477-1484

[9]

Fallarino F, 2003, ADV EXP MED BIOL, V527, P183

[10]

The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor ζ-chain and induce a regulatory phenotype in naive T cells [J].

Fallarino, Francesca ;

Grohmann, Ursula ;

You, Sylvaine ;

McGrath, Barbara C. ;

Cavener, Douglas R. ;

Vacca, Carmine ;

Orabona, Ciriana ;

Bianchi, Roberta ;

Belladonna, Maria L. ;

Volpi, Claudia ;

Santamaria, Pere ;

Fioretti, Maria C. ;

Puccetti, Paolo .

JOURNAL OF IMMUNOLOGY, 2006, 176 (11) :6752-6761

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