Molecular and functional heterogeneity of T regulatory cells

Naturally occurring CD4+ T regulatory (Treg) cells are produced during maturation in the thymus and have a mandatory role in maintaining homeostasis and immune quiescence. Development and function of Treg cells depends on the transcription factor forkhead box P3 (Foxp3), which is necessary and sufficient for Treg cell function. Currently emerging evidence indicates Treg cells display molecular and functional heterogeneity and can be categorized into naïve and effector- or memory-like cells, which can produce effector cytokines supporting the idea that Treg cells retain plasticity. The role of Treg cells that acquire these properties remains unclear and is currently under intense investigation. In this review, we summarize recent advances on the differentiation of effector- or memory-like Treg cells, the impact of the cytokine milieu on the molecular and functional heterogeneity of Treg cells, and the clinical implications of the heterogeneity and specialization of Treg cells.