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

Abstract : 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.
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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, Nature Publishing Group, 2010, ⟨10.1038/ni.1874⟩. ⟨hal-00531148⟩

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