Regulatory T cells (Treg cells) are known to have intracellular signaling patterns different from those of their conventional T cell counterparts. In the Proceedings of the National Academy of Sciences USA, Benoist and colleagues investigate the basis of this altered signaling. They confirm that signaling via various pathways emanating from the T cell antigen receptor (TCR) on Treg cells is considerably diminished compared with that of conventional T cells. This impairment is not explained by increased expression of signal modulators such as CD5, PD-1, or CTLA4 in Treg cells nor indeed by differences in expression of the TCR itself. However, diminished phosphorylation is not a global characteristic of Treg cells, because signaling via certain cytokines, such as type I interferons, IL-2 and (in part) IL-6, is instead enhanced. Treg cells are therefore 'wired' to be relatively unresponsive via the TCR but more sensitive to particular cytokines.

Proc. Natl. Acad. Sci. USA (20 October 2015) doi:10.1073/pnas.1520393112