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

SP Cobbold, E Adams, CA Farquhar… - Proceedings of the …, 2009 - National Acad Sciences
SP Cobbold, E Adams, CA Farquhar, KF Nolan, D Howie, KO Lui, PJ Fairchild, AL Mellor
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
Infectious tolerance describes the process of CD4+ regulatory T cells (Tregs) converting
naļve 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 …
Infectious tolerance describes the process of CD4+ regulatory T cells (Tregs) converting naļve 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.
National Acad Sciences