Continuous requirement for the T cell receptor for regulatory T cell function

Foxp3(+) regulatory T cells (T(reg) cells) maintain immunological tolerance and their deficiency results in fatal multi-organ autoimmunity. Although heightened T cell receptor (TCR) signaling is critical for the differentiation of T(reg) cells, the role of TCR signaling in T(reg) cell function remains largely unknown. Here we demonstrate inducible ablation of the TCR results in T(reg) cell dysfunction which cannot be attributed to impaired Foxp3 expression, decreased expression of T(reg) cell signature genes or altered ability to sense and consume interleukin 2. Rather, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated T(reg) cell transcriptional signature. Our results reveal a critical role for the TCR in T(reg) cell suppressor capacity.