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

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

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
Pages (from-to)	12055-12060
Number of pages	5
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
Publication status	Published - 21 Jul 2009

Keywords

Amino acid catabolism
Foxp3
mTOR inhibitor
Rapamycin
Regulatory T cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.0903919106

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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

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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, mTOR inhibitor, Rapamycin, Regulatory T cells",

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",

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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

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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 - mTOR inhibitor

KW - Rapamycin

KW - Regulatory T cells

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

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ER -

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

Abstract

Keywords

UN SDGs

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