Continuous requirement for the TCR in regulatory T cell function

Regulatory T cells help to keep adaptive immunity in check. Rudensky and colleagues show that these cells continuously require TCR signaling to maintain their cellular identity and homeostasis and to exert their suppressive ability. Foxp3+ regulatory T cells (Treg cells) maintain immunological tolerance, and their deficiency results in fatal multiorgan autoimmunity. Although heightened signaling via the T cell antigen receptor (TCR) is critical for the differentiation of Treg cells, the role of TCR signaling in Treg cell function remains largely unknown. Here we demonstrated that inducible ablation of the TCR resulted in Treg cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of Treg cell signature genes or altered ability to sense and consume interleukin 2 (IL-2). Instead, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated Treg cell transcriptional signature. Our results reveal a critical role for the TCR in the suppressor capacity of Treg cells.