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Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self

Nature Immunology volume 2, pages 1032–1039 (2001)Cite this article

Abstract

Expression of peripheral antigens in the thymus has been implicated in T cell tolerance and autoimmunity. Here we identified medullary thymic epithelial cells as being a unique cell type that expresses a diverse range of tissue-specific antigens. We found that this promiscuous gene expression was a cell-autonomous property of medullary epithelial cells and was maintained during the entire period of thymic T cell output. It may facilitate tolerance induction to self-antigens that would otherwise be temporally or spatially secluded from the immune system. However, the array of promiscuously expressed self-antigens appeared random rather than selected and was not confined to secluded self-antigens.

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Figure 1: Promiscuous expression of tissue-specific genes by distinct thymic stromal cells.
Figure 2: Expression of pancreatic autoantigens in mTECs versus thymic or splenic DCs.
Figure 3: Protein expression of tissue-antigens by mTECs.
Figure 4: Promiscuous gene expression by subsets of mTECs.
Figure 5: Promiscuous gene expression during ontogeny.
Figure 6: Promiscuous expression of a fetal tissue antigen.
Figure 7: Promiscuous gene expression in RAG-2−/− mice.
Figure 8: Expression of SAP in mTECs is sufficient, but not necessary for T cell tolerance.

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Acknowledgements

We thank J. Gotter, J. Trotter and W. van Ewijk for helpful suggestions; M. B. Pepys (Royal Free and University College Medical School, London) for providing purified mouse SAP and SAP-deficient mice; B. Arnold, T. Boehm, R. Ganss, J. Trotter, T. Schlake and B. van den Eynde for reagents and mice; and S. Hoeflinger, S. Fuchs and K. Hexel for assistance. Supported by the Deutsche Forschungsgemeinschaft (grants Ky7/6-1 and the SFB 405 to B. K. and LK1228/1-1 to L. K.) and the German Cancer Research Center.

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  1. Ludger Klein

    Present address: Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 1, Jimmy Fund Way, Boston, MA, 02115, USA

Authors and Affiliations

  1. Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, INF 280, D-69120, Germany

    Jens Derbinski, Antje Schulte, Bruno Kyewski & Ludger Klein

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Correspondence to Bruno Kyewski.

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Derbinski, J., Schulte, A., Kyewski, B. et al. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol 2, 1032–1039 (2001). https://doi.org/10.1038/ni723

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