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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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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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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DOI: https://doi.org/10.1038/ni723