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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.

Original publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





12055 - 12060


Adoptive Transfer, Amino Acids, Essential, Animals, Cell Proliferation, Cell Survival, Dendritic Cells, Epitopes, Forkhead Transcription Factors, Immune Tolerance, Lymphocyte Activation, Mice, Phosphoinositide-3 Kinase Inhibitors, Protein Kinases, Protein-Serine-Threonine Kinases, Signal Transduction, Sirolimus, Skin Transplantation, T-Lymphocytes, Regulatory, TOR Serine-Threonine Kinases, Transforming Growth Factor beta