Abstract

Although the development of regulatory T cells (T_reg cells) in the thymus is defined by expression of the lineage marker Foxp3, the precise function of Foxp3 in T_reg cell lineage commitment is unknown. Here we examined T_reg cell development and function in mice with a Foxp3 allele that directs expression of a nonfunctional fusion protein of Foxp3 and enhanced green fluorescent protein (Foxp3^EGFP). Thymocyte development in Foxp3^EGFP male mice and Foxp3^EGFP/+ female mice recapitulated that of wild-type mice. Although mature EGFP⁺ CD4⁺ T cells from Foxp3^EGFP mice lacked suppressor function, they maintained the characteristic T_reg cell 'genetic signature' and failed to develop from EGFP^- CD4⁺ T cells when transferred into lymphopenic hosts, indicative of their common ontogeny with T_reg cells. Our results indicate that T_reg cell effector function but not lineage commitment requires the expression of functional Foxp3 protein.

NOTE: In the version of this article initially published online, the 'Foxp2^EGFP' and 'Foxp2^EGFP' labels in Figure 7 are incorrect. The correct labels should be 'Foxp3^EGFP' and 'Foxp3^EGFP', respectively. Also, Supplementary Tables 1-3 truncated early. The errors have been corrected for all versions of the article.

1. Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, The David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California 90095, USA.
2. Division of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
3. Department of Human Genetics, The David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California 90095, USA.

Correspondence to: Talal A Chatila¹ e-mail: tchatila@mednet.ucla.edu

Correspondence to: Calvin B Williams² e-mail: cwilliam@mcw.edu

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