Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice

Mice lacking the transcription factor Foxp3 (Foxp3(-)) lack regulatory T (T-reg) cells and develop fatal autoimmune pathology. In Foxp3(-) mice, many activated effector T cells express self-reactive T cell receptors that are expressed in T-reg cells in wild-type mice. Thus, in wild-type mice, most self-reactive thymocytes escaping negative selection are diverted into the T-reg lineage, and whether T-reg cells are critical in self-tolerance in wild-type mice remains unknown. Here, acute in vivo ablation of T-reg cells demonstrated a vital function for T-reg cells in neonatal and adult mice. We suggest that self-reactive T cells are continuously suppressed by T-reg cells and that when suppression is relieved, self-reactive T cells become activated and facilitate accelerated maturation of dendritic cells.