Impaired T cell receptor signaling in Foxp3+ CD4 T cells.

Dominant tolerance to autoantigens is primarily achieved through the action of the CD4(+)CD25(+)Foxp3(+) subset of T cells, which have the capability of suppressing autoreactive T cells that have escaped deletion during thymic selection. The essential role of the forkhead/winged-helix transcription factor Foxp3 in the development and function of these cells has been well documented. What is less clear is the role of Foxp3 in the altered TCR signaling that is seen in Tregs. We have used a Foxp3 transgenic mouse line to demonstrate that Foxp3 expression correlates with attenuated TCR signaling, and that the deficit in Foxp3-transgenic CD4 T cells, as well as in CD4(+)CD25(+) Tregs, affects multiple biochemical pathways.