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

Stephen P Cobbold1, Elizabeth Adams, Claire A Farquhar

  • 1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom. stephen.cobbold@path.ox.ac.uk

Proceedings of the National Academy of Sciences of the United States of America
|July 2, 2009
PubMed

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-beta.

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