Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them?

Regulatory T cells (Tregs) are critical regulators of peripheral immune tolerance. Treg insufficiency can lead to autoimmune disorders, including type 1 diabetes (T1D). Increasing evidence in mouse models of T1D, as well as other autoimmune disorders, suggests that there are defects in Treg-mediated suppression. Indeed, whereas Treg frequency in the peripheral blood of T1D patients is unaltered, their suppressive abilities are diminished compared with Tregs in healthy controls. Although expression of the transcription factor Foxp3 is a prerequisite for Treg development and function, there are many additional factors that can alter their stability, survival, and function. Much has been learned in other model systems, such as tumors, about the mechanism and pathways that control Treg stability and function. This review poses the question of whether we can use these findings to develop new therapeutic approaches that might boost Treg stability, survival, and/or function in T1D and possibly other autoimmune disorders.