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¹ Department of Immunology, University of Washington, Seattle, WA 98195
² Department of Biological Structure, University of Washington, Seattle, WA 98195
³ Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195

CORRESPONDENCE Jason D. Fontenot: jfontenot{at}rockefeller.edu OR Alexander Y. Rudensky: aruden{at}u.washington.edu

Thymectomy of neonatal mice can result in the development of autoimmune pathology. It has been proposed that thymic output of regulatory T (T reg) cells is delayed during ontogeny and that the development of autoimmune disease in neonatally thymectomized mice is caused by the escape of self-reactive T cells before thymectomy without accompanying T reg cells. However, the kinetics of T reg cell production within the thymus during ontogeny has not been assessed. We demonstrate that the development of Foxp3-expressing T reg cells is substantially delayed relative to nonregulatory thymocytes during ontogeny. Based on our data, we speculate that induction of Foxp3 in developing thymocytes and, thus, commitment to the T reg cell lineage is facilitated by a signal largely associated with the thymic medulla.

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