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Checkpoints in the Development of Thymic Cortical Epithelial Cells¹

Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, United Kingdom

In the thymus, interactions between immature thymocytes and thymic epithelial cells (TECs) regulate the development and selection of self-tolerant MHC-restricted T cells. Despite the importance of cortical (cTEC) and medullary (mTEC) thymic epithelial cells in fostering T cell production, events in TEC development are still unclear. Although precursor-product relationships during mTEC development have been reported, and some genetic regulators of mTEC development have been identified, stages in cTEC development occurring downstream of recently identified bipotent cTEC/mTEC progenitors remain poorly defined. In this study, we combine analysis of differentiation, proliferation, and gene expression of TECs in the murine thymus, that has enabled us to identify cTEC progenitors, define multiple stages in cTEC development, and identify novel checkpoints in development of the cTEC lineage. We show an essential requirement for FoxN1 in the initial development of cTEC from bipotent progenitors, and demonstrate a stage-specific requirement for CD4^–8^– thymocytes in later stages of cTEC development. Collectively, our data establish a program of cTEC development that should provide insight into the formation and function of the thymic cortex for T cell development.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Medical Research Council Programme Grant (to E.J.J. and G.A.), and the European Union-funded FP6 Thymaide Integrated Project.

² S.S. and G.E.D. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Graham Anderson, Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K. E-mail address: g.anderson{at}bham.ac.uk

⁴ Abbreviations used in this paper: mTEC, medullary thymic epithelial cell; TEC, thymic epithelial cell; cTEC, cortical TEC subset; AIRE, autoimmune regulator gene; FTOC, fetal thymic organ culture; WT, wild type; DN, double negative.

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The JI 2009 182: 1-2. [Full Text]  

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