¹Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Correspondence: Lauren E Mays, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 125 S. 31st Street, Philadelphia, PA 19104, USA.
Tel: +1 215 898 8359; Fax: +1 215 898 6588 E-mail: maysle@mail.med.upenn.edu; Youhai H Chen, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 713 Stellar-Chance Labs, 422 Curie Blvd., Philadelphia, PA 19104, USA.
Tel: +1 215 898 4671; Fax: +1 215 573 3434 E-mail: yhc@mail.med.upenn.edu

Abstract

Central tolerance in the thymus is the primary mechanism for deleting autoreactive T cells. Despite this, escape of self-reactive T lymphocytes into the periphery reveals the threat of autoimmunity. To compensate for its imperfection, the thymus also produces a naturally occurring subset of Foxp3+ CD4+ CD25+ regulatory T cells with suppressive function, capable of controlling autoreactive cells. Foxp3 (forkhead box P3), the lineage-specific marker for this subset of cells, is crucial to their thymic development and peripheral function, and yet the transcriptional program driven by Foxp3 was until now largely undefined. Emerging evidence has provided insight into its role: from the ability of Foxp3 to cooperate with other transcription factors such as NFAT, to the genome-wide characterization of target genes directly bound and regulated by Foxp3. Here we discuss the discovery of naturally occurring regulatory T cells – their phenotype, development, maintenance, and function – largely as they are defined by the lineage-specific marker, Foxp3.