Regulatory T cells require constant reassurance

Regulatory T (T_Reg) cells require T cell receptor (TCR) signalling for their development, but it has been unclear how TCR signals contribute to their functions in the periphery. Vahl et al. used an inducible deletion system to specifically ablate TCR expression on mature peripheral T_Reg cells in mice. They found that TCR ablation did not affect T_Reg cell expression of forkhead box P3 (FOXP3) or epigentic remodelling at key T_Reg cell-associated gene loci. TCR ablation also did not affect T_Reg cell expression of molecules that are required for lymph node homing. However, T_Reg cells lacking TCRs did not undergo homeostatic proliferation and were progressively lost from the periphery. Furthermore, TCR-deficient T_Reg cells lost their expression of key anti-inflammatory mediators, including interleukin-10. Finally, ablation of TCR expression on T_Reg cells led to the spontaneous development of colitis and splenomegaly in mice. Therefore, continuous restimulation through the TCR seems to be essential for the suppressive functions of T_Reg cells.