title: Developmental regulation of Foxp3 expression during ontogeny.
abstract: 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.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195, USA. jfontenot@rockefeller.edu
authors.forename: Jason D
authors.initials: JD
authors.lastname: Fontenot
authors.forename: James L
authors.initials: JL
authors.lastname: Dooley
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Farr
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D013950:Thymus Gland / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse