Origin of Foxp3+ Tregs. During thymic ontogeny, double positive (CD4+CD8+) thymocytes with low affinity for self-peptide + self-MHC undergo positive selection, becoming single positive CD8+ or CD4+ thymocytes which eventually are exported into the peripheral lymphoid compartment as naïve T cells. Under certain conditions (see figure 2 for more details), these naïve T cells can be induced to express Foxp3, and these cells are known as pTregs (for Tregs of peripheral origin). Double positive thymocytes with moderate affinity for self-peptide + self-MHC are induced to express Foxp3, and these cells, known as tTregs because of their thymic origin, are exported into the periphery as “fully formed” Tregs. Abbreviations: Foxp3+ Tregs, Foxp3 positive regulatory T cells; MHC, major histocompatibility complex; tTregs, thymic-derived Tregs; IL, interleukin; TCR, T cell receptor; pTreg, induced peripheral regulatory T cells.