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Nat Immunol. 2007 Apr;8(4):351-8. Epub 2007 Feb 25.

Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells.

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Research Institute of Molecular Pathology, 1030 Vienna, Austria.


The parameters specifying whether autoreactive CD4(+) thymocytes are deleted (recessive tolerance) or differentiate into regulatory T cells (dominant tolerance) remain unresolved. Dendritic cells directly delete thymocytes, partly through cross-presentation of peripheral antigens 'promiscuously' expressed in medullary thymic epithelial cells (mTECs) positive for the autoimmune regulator Aire. It is unclear if and how mTECs themselves act as antigen-presenting cells during tolerance induction. Here we found that an absence of major histocompatibility class II molecules on mTECs resulted in fewer polyclonal regulatory T cells. Furthermore, targeting of a model antigen to Aire(+) mTECs led to the generation of specific regulatory T cells independently of antigen transfer to dendritic cells. Thus, 'routing' of mTEC-derived self antigens may determine whether specific thymocytes are deleted or enter the regulatory T cell lineage.

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