Influence of FOXP3 on CD4+CD25+ regulatory T cells

FOXP3, a member of the forkhead family of transcriptional regulatory proteins, is expressed predominantly in CD4(+)CD25(+) regulatory T cells. These cells are vital for maintaining peripheral tolerance. A lack of FOXP3 results in severe lymphoproliferative disease and autoimmunity in both mouse and humans, which is the result of an absence of CD4(+)CD25(+)FOXP3(+) regulatory cells. This review discusses the role that this protein plays in the commitment and function of regulatory T cells and its characteristics of FOXP3. We then discuss how, in humans, the induction of FOXP3 in nonregulatory CD4(+) T cells can result in the generation of regulatory T cells in the periphery. A finding that has implications on both how autoimmunity is regulated in vivo as well an impact on the development of therapeutic interventions for the treatment of autoimmunity.