Journal
NATURE IMMUNOLOGY
Volume 8, Issue 4, Pages 351-358Publisher
NATURE RESEARCH
DOI: 10.1038/ni1444
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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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