Portal de Periódicos da CAPES

Autonomous role of medullary thymic epithelial cells in central CD4+ T cell tolerance

2010; Nature Portfolio; Volume: 11; Issue: 6 Linguagem: Inglês

10.1038/ni.1874

1529-2916

Maria Hinterberger, Martin Aichinger, Olivia Prazeres da Costa, David Voehringer, Reinhard Hoffmann, Ludger Klein,

Immune Cell Function and Interaction

Medullary thymic epithelial cells are essential to the establishment of central tolerance by expressing peripheral tissue antigens. Klein and co-workers now show that these cells also mediate clonal deletion of CD4+ T cells. Medullary thymic epithelial cells (mTECs) serve an essential function in central tolerance by expressing peripheral-tissue antigens. These antigens may be transferred to and presented by dendritic cells (DCs). Therefore, it is unclear whether mTECs, in addition to being an antigen reservoir, also serve a mandatory function as antigen-presenting cells. Here we diminished major histocompatibility complex (MHC) class II on mTECs through transgenic expression of a 'designer' microRNA specific for the MHC class II transactivator CIITA (called 'C2TA' here). This resulted in an enlarged polyclonal CD4+ single-positive compartment and, among thymocytes specific for model antigens expressed in mTECs, enhanced selection of regulatory T cells (Treg cells) at the expense of deletion. Our data document an autonomous contribution of mTECs to both dominant and recessive mechanisms of CD4+ T cell tolerance and support an avidity model of Treg cell development versus deletion.