title: Development of thymic microenvironments in vitro is oxygen-dependent and requires permanent presence of T-cell progenitors.
abstract: Development of a mature T-cell repertoire in the thymus depends on lympho-stromal interaction between thymocytes and stromal cells. To facilitate intercellular contact, the epithelium in the thymus has differentiated into a unique three-dimensionally (3D)-oriented network. Here we analyze factors influencing induction and maintenance of the 3D configuration of the epithelial network in fetal thymic lobes in vitro. We show that the 3D configuration of the thymic stroma depends on (a) the oxygen pressure in vitro and (b) permanent physical contact between stromal cells and developing thymocytes. This latter feature is demonstrated by incubation of fetal thymic lobes with deoxyguanosine (d-Guo), inducing a 2D-organized thymic stroma, with thymic cysts appearing. Reconstitution of d-Guo-treated lobes with a limited number of flow-sorted T-cell progenitors restores the 3D configuration of the thymic epithelium, but only at high oxygen pressure. This study underlines the plasticity of thymic epithelium and shows that the unique organization of the thymic epithelium is dependent on both oxygen and crosstalk signals derived from developing thymocytes.
authors.affiliation: Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands. vanewijk@lumc.nl
authors.forename: Wilfred T V
authors.initials: WT
authors.lastname: Germeraad
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Manami
authors.initials: M
authors.lastname: Itoi
authors.forename: Yufei
authors.initials: Y
authors.lastname: Jiang
authors.forename: Takashi
authors.initials: T
authors.lastname: Amagai
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Katsura
authors.forename: Willem
authors.initials: W
authors.lastname: van Ewijk
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000502:physiology*; D010313:Partial Pressure; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology
chemical_list: D018960:Hyaluronan Receptors; D015375:Receptors, Interleukin-2; D010100:Oxygen