CD4⁺ CD25⁺ regulatory T cells (Tregs) expressing the lineage-specific marker Foxp3 represent an important regulatory T cell that is essential for maintaining peripheral tolerance. Although it was believed that Treg development is solely dependent on the thymus, accumulating evidence demonstrates that Tregs can also be induced in the periphery. Considering the various origins of peripherally developed CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells, it seems likely that multiple factors are involved in the peripheral generation of Tregs.