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

Ludger Klein (1) , Maria Hinterberger (1) , Martin Aichinger (1) , Olivia Prazeres da Costa (1) , David Voehringer (1) , Reinhard Hoffmann (1)

1 Institute for Immunology

Medullary thymic epithelial cells (mTECs) serve an essential function in central tolerance through expressing peripheral tissue-antigens. These antigens may be transferred to and presented by dendritic cells. Therefore, it is unclear whether mTECs, besides being an 'antigen-reservoir', also serve a mandatory function as antigen presenting cells. Here, we reduced MHC class II on mTECs through transgenic expression of a C2TA-specific 'designer miRNA'. 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) at the expense of deletion. Our data document an autonomous contribution of mTECs to dominant and recessive mechanisms of CD4+ T cell tolerance and support an avidity model of Treg development versus deletion.

Mots clés: Tolerance; Antigen presentation

Ludger Klein, Maria Hinterberger, Martin Aichinger, Olivia Prazeres da Costa, David Voehringer, et al.. Autonomous role of medullary thymic epithelial cells in central CD4+ T cell tolerance. Nature Immunology, 2010, ⟨10.1038/ni.1874⟩. ⟨hal-00531148⟩