Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 29, Pages 12055-12060Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0903919106
Keywords
amino acid catabolism; foxp3; mTOR inhibitor; regulatory T cells; rapamycin
Categories
Funding
- National Institutes of Health [DK47119, ES08681, AI44219]
- Carlos and Marguerite Mason Trust
- Medical Research Council [G7904009, G0802538] Funding Source: researchfish
- MRC [G0802538, G7904009] Funding Source: UKRI
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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.
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