title: 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 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 (T(reg) 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 T(reg) cell development versus deletion.
authors.affiliation: Institute for Immunology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Hinterberger
authors.forename: Martin
authors.initials: M
authors.lastname: Aichinger
authors.forename: Olivia
authors.initials: O
authors.lastname: Prazeres da Costa
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009687:Nuclear Proteins; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology*; D015534:Trans-Activators
chemical_list: C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators