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N aturally arising CD4⁺ regulatory T cells, which engage in the maintenance of immunologic self-tolerance, specifically express FOXP3, which encodes a transcription-repressor protein. Genetic defects in FOXP3 cause IPEX, an X-linked autoimmune/inflammatory syndrome. With FOXP3 as a specific marker for regulatory CD4⁺ T cells in humans, it is now possible to determine their origin and developmental pathway .