Control of Regulatory T Cell Development by the Transcription Factor <i>Foxp3</i>

TLDR

Regulatory T cells maintain self‑tolerance by suppressing self‑reactive lymphocytes, yet the molecular mechanisms underlying their development remain poorly understood. Retroviral delivery of Foxp3 reprograms naïve T cells into regulatory T‑cell–like cells that resemble naturally occurring CD4⁺ Tregs. Foxp3 is specifically expressed in natural CD4⁺ regulatory T cells and is essential for their development, as shown by its ability to convert naïve T cells into regulatory phenotypes.

Abstract

Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.