Loss of the transcription factor Foxp3 in Treg cells has been noted in various inflammatory conditions. In Immunity, Bluestone and colleagues use an experimental autoimmune encephalitis (EAE) model to show that antigen-driven activation and inflammation selectively promotes Foxp3 instability in autoreactive Treg cells. Antigen-driven activation in an inflammatory environment results in downregulation of Foxp3 transcription in Treg cells that had high Foxp3 expression before EAE induction. Formerly Treg cells that have lost Foxp3 expression produce interferon-γ in amounts similar to those observed in pathogenic effector T cells and induce EAE after adoptive transfer. Supplementation with IL-2 stabilizes Foxp3 expression in antigen-specific Treg cells and protects mice from disease. Thus, the stability of antigen-specific Treg cells might be important for the course and control of autoimmunity.

Immunity 39, 949–962 (2013)