A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3

The random generation of antigen receptors in developing lymphocytes results in a considerable risk of autoimmunity. Regulatory T cells (T-reg cells) act in a dominant, trans-acting way to actively suppress immune activation and maintain immune tolerance. Here, we discuss the principal advances in our understanding of the molecular mechanisms of T-reg cell development and function with particular emphasis on the forkhead transcription factor Foxp3. Accumulating evidence suggests that T-reg cells represent a dedicated T cell lineage and that Foxp3 functions as the T-reg cell lineage specification factor. The aggressive early- onset lymphoproliferative syndrome resulting from Foxp3 deficiency identifies T-reg cells as vital mediators of immunological tolerance to self and Foxp3 as the mediator of the genetic mechanism of dominant tolerance.