title: Fluorochrome-based definition of naturally occurring Foxp3(+) regulatory T cells of intra- and extrathymic origin.
abstract: Under physiological conditions, studies on the biology of naturally induced Foxp3(+) Treg cells of intra- and extrathymic origin have been hampered by the lack of unambiguous markers to discriminate the mature progeny of such developmental Treg-cell sublineages. Here, we report on experiments in double-transgenic mice, in which red fluorescent protein (RFP) is expressed in all Foxp3(+) Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3(+) Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP(+) GFP(+) ) and extrathymic (RFP(+) GFP(-) ) origin in otherwise unmanipulated mice. These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3(+) Treg cells residing in peripheral lymphoid tissues of steady-state mice. Furthermore, we provide evidence that intra- and extrathymically induced Foxp3(+) Treg cells represent distinct phenotypic and functional sublineages.
authors.affiliation: Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.
authors.forename: Cathleen
authors.initials: C
authors.lastname: Petzold
authors.forename: Nadine
authors.initials: N
authors.lastname: Steinbronn
authors.forename: Marcus
authors.initials: M
authors.lastname: Gereke
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.forename: Sonja
authors.initials: S
authors.lastname: Schallenberg
authors.forename: Karsten
authors.initials: K
authors.lastname: Kretschmer
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology*; D008164:Luminescent Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D000097573:Red Fluorescent Protein
chemical_list: D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C498833:Foxp3 protein, mouse
keywords: Fluorochrome reporter; Foxp3; Regulatory T cells; T-cell development