title: Dendritic cells in the thymus contribute to T-regulatory cell induction.
abstract: Central tolerance is established through negative selection of self-reactive thymocytes and the induction of T-regulatory cells (T(R)s). The role of thymic dendritic cells (TDCs) in these processes has not been clearly determined. In this study, we demonstrate that in vivo, TDCs not only play a role in negative selection but in the induction of T(R)s. TDCs include two conventional dendritic cell (DC) subtypes, CD8(lo)Sirpalpha(hi/+) (CD8(lo)Sirpalpha(+)) and CD8(hi)Sirpalpha(lo/-) (CD8(hi)Sirpalpha(-)) [corrected] which have different origins. We found that the CD8(hi)Sirpalpha(+) DCs represent a conventional DC subset that originates from the blood and migrates into the thymus. Moreover, we show that the CD8(lo)Sirpalpha(+) DCs demonstrate a superior capacity to induce T(R)s in vitro. Finally, using a thymic transplantation system, we demonstrate that the DCs in the periphery can migrate into the thymus, where they efficiently induce T(R) generation and negative selection.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia. proietto@wehi.edu.au
authors.forename: Anna I
authors.initials: AI
authors.lastname: Proietto
authors.forename: Serani
authors.initials: S
authors.lastname: van Dommelen
authors.forename: Penghui
authors.initials: P
authors.lastname: Zhou
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rizzitelli
authors.forename: Angela
authors.initials: A
authors.lastname: D'Amico
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Steptoe
authors.forename: Shalin H
authors.initials: SH
authors.lastname: Naik
authors.forename: Mireille H
authors.initials: MH
authors.lastname: Lahoud
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Li
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002465:Cell Movement; D018925:Chemokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D011971:Receptors, Immunologic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D018845:CD11 Antigens; D016827:CD8 Antigens; D018925:Chemokines; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; D010047:Ovalbumin