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

K Aschenbrenner, LM D'Cruz, EH Vollmann… - Nature …, 2007 - nature.com
K Aschenbrenner, LM D'Cruz, EH Vollmann, M Hinterberger, J Emmerich, LK Swee…
Nature immunology, 2007nature.com
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 …
Abstract
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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