title: Development and activation of regulatory T cells in the human fetus.
abstract: There is an increasing amount of knowledge on the functional properties of regulatory T cells (Treg) in the adult immune system, but data on the generation and function of these cells during human embryonic development are scarce. In this study, we show that in the fetal thymus, double-positive cells initiate expression of CD25, GITR, CTLA4 and CD122 during their transition from the CD27- to the CD27+ stage. Moreover, CD4+CD25+ fetal thymocytes already have the potential to suppress proliferation of CD25- cells. After leaving the thymus, FoxP3+CD4+CD25+ Treg enter the fetal lymph nodes and spleen, where they acquire a primed/memory phenotype. A model is proposed for the development of human fetal Treg that encompasses two sequential maturation steps: initiation of a regulatory phenotype and suppressive activity in the thymus; and subsequent activation within the peripheral lymphoid organs. Upon activation, FoxP3+CD4+CD25+ Treg suppress potentially deleterious responses by autoreactive lymphocytes and maintain homeostasis within the developing fetus.
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Cupedo
authors.forename: Maho
authors.initials: M
authors.lastname: Nagasawa
authors.forename: Kees
authors.initials: K
authors.lastname: Weijer
authors.forename: Bianca
authors.initials: B
authors.lastname: Blom
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology; D011247:Pregnancy; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2