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

Stephen P. Cobbold; Elizabeth Adams; Claire A. Farquhar; Kathleen F. Nolan; Duncan Howie; Kathy O. Lui; Paul J. Fairchild; Andrew L. Mellor; David Ron; Herman Waldmann

doi:10.1073/pnas.0903919106

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

Stephen P. Cobbold, Elizabeth Adams, Claire A. Farquhar, Kathleen F. Nolan, Duncan Howie, Kathy O. Lui, Paul J. Fairchild, Andrew L. Mellor, David Ron, Herman Waldmann

Infectious Disease

Research output: Contribution to journal › Article › peer-review

267 Scopus citations

Abstract

Infectious tolerance describes the process of CD4⁺ regulatory T cells (Tregs) converting naïve 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-β.

Original language	English (US)
Pages (from-to)	12055-12060
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	106
Issue number	29
DOIs	https://doi.org/10.1073/pnas.0903919106
State	Published - Jul 21 2009

Keywords

Amino acid catabolism
Foxp3
Rapamycin
Regulatory T cells
mTOR inhibitor

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.0903919106

Cite this

Cobbold, S. P., Adams, E., Farquhar, C. A., Nolan, K. F., Howie, D., Lui, K. O., Fairchild, P. J., Mellor, A. L., Ron, D., & Waldmann, H. (2009). Infectious tolerance via the consumption of essential amino acids and mTOR signaling. Proceedings of the National Academy of Sciences of the United States of America, 106(29), 12055-12060. https://doi.org/10.1073/pnas.0903919106

@article{5229a26a661f44a88cc534a8c852cc3a,

title = "Infectious tolerance via the consumption of essential amino acids and mTOR signaling",

abstract = "Infectious tolerance describes the process of CD4+ regulatory T cells (Tregs) converting na{\"i}ve 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-β.",

keywords = "Amino acid catabolism, Foxp3, Rapamycin, Regulatory T cells, mTOR inhibitor",

author = "Cobbold, {Stephen P.} and Elizabeth Adams and Farquhar, {Claire A.} and Nolan, {Kathleen F.} and Duncan Howie and Lui, {Kathy O.} and Fairchild, {Paul J.} and Mellor, {Andrew L.} and David Ron and Herman Waldmann",

year = "2009",

month = jul,

day = "21",

doi = "10.1073/pnas.0903919106",

language = "English (US)",

volume = "106",

pages = "12055--12060",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "29",

}

TY - JOUR

T1 - Infectious tolerance via the consumption of essential amino acids and mTOR signaling

AU - Cobbold, Stephen P.

AU - Adams, Elizabeth

AU - Farquhar, Claire A.

AU - Nolan, Kathleen F.

AU - Howie, Duncan

AU - Lui, Kathy O.

AU - Fairchild, Paul J.

AU - Mellor, Andrew L.

AU - Ron, David

AU - Waldmann, Herman

PY - 2009/7/21

Y1 - 2009/7/21

N2 - Infectious tolerance describes the process of CD4+ regulatory T cells (Tregs) converting naïve 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-β.

AB - Infectious tolerance describes the process of CD4+ regulatory T cells (Tregs) converting naïve 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-β.

KW - Amino acid catabolism

KW - Foxp3

KW - Rapamycin

KW - Regulatory T cells

KW - mTOR inhibitor

UR - http://www.scopus.com/inward/record.url?scp=67749091321&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67749091321&partnerID=8YFLogxK

U2 - 10.1073/pnas.0903919106

DO - 10.1073/pnas.0903919106

M3 - Article

C2 - 19567830

AN - SCOPUS:67749091321

SN - 0027-8424

VL - 106

SP - 12055

EP - 12060

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 29

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this