Development of thymic microenvironments in vitro is oxygen-dependent and requires permanent presence of T-cell progenitors

Wilfred T.V. Germeraad, Hiroshi Kawamoto, Manami Itoi, Yufei Jiang, Takashi Amagai, Yoshimoto Katsura, Willem Van Ewijk

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1225-1235
Number of pages11
JournalJournal of Histochemistry and Cytochemistry
Volume51
Issue number9
DOIs
Publication statusPublished - 01-09-2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Histology

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