Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance.
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.
Hinterberger
Maria
M
Institute for Immunology, Ludwig-Maximilians-Universität, Munich, Germany.
Aichinger
Martin
M
Prazeres da Costa
Olivia
O
Voehringer
David
D
Hoffmann
Reinhard
R
Klein
Ludger
L
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
C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators