Functional stability of Foxp3+ regulatory T cells

Significant evidence demonstrates that CD4+ regulatory T cells (Treg) expressing the Forkhead box P3 (Foxp3) transcription factor are a distinct lineage of CD4+ T cells that are essential for maintaining self-tolerance and modulating immunity to various nonself-antigens under changing inflammatory settings. Stable Foxp3 expression ensures Treg function in a variety of inflammatory contexts. However, the model of Treg cells as a stable, long-lived lineage is controversial. Whereas some studies have observed long-lived Treg function, recent studies suggest that Treg cells adapt to microenvironmental changes and consequently manifest functional plasticity by reprogramming into inflammatory T cells. Here, we review the evidence addressing the functional stability or plasticity of Foxp3+ Treg cells and the implications for immune homeostasis and disease.