Treg development occurs via a two-step process. In step 1, signals through the T cell receptor and costimulation via CD28 initiate a Treg developmental program that is dependent on the NFkB signaling pathway. Notably, signals through CARMA1 and C-REL initiate a Treg progenitor in which cytokine signaling such as IL-2 (step 2) via STAT5 turns on Foxp3. Herein, we discuss in detail the molecular requirement for natural regulatory T cell development. |