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1: Nat Immunol. 2007 Apr;8(4):351-8. Epub 2007 Feb 25.
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Comment in:
Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells.

Aschenbrenner K, D'Cruz LM, Vollmann EH, Hinterberger M, Emmerich J, Swee LK, Rolink A, Klein L.

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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PMID: 17322887 [PubMed - indexed for MEDLINE]