Regulatory T cell plasticity: beyond the controversies

Forkhead box P3 (Foxp3)(+) regulatory T (Treg) cells represent a distinct cell lineage that is committed to suppressive functions, whose stable differentiation state ensures the robustness of self-tolerance and immune homeostasis in a changing environment. Recent studies have challenged this notion and suggest that Treg cells retain developmental plasticity to be reprogrammed to Foxp3(-) helper T cells in response to extrinsic perturbations such as inflammation and lymphopenia. This issue of Treg cell plasticity, however, remains controversial because other recent reports argue against the plasticity phenomena. Here, I propose that the controversies can be resolved by considering the heterogeneity model of plasticity, which hypothesizes that the observed plasticity does not reflect lineage reprogramming of Treg cells but rather a minor population of uncommitted Foxp3(+) T cells.