title: Autonomous versus dendritic cell-dependent contributions of medullary thymic epithelial cells to central tolerance.
abstract: Promiscuous expression of 'peripheral' tissue-restricted antigens (TRAs) by medullary thymic epithelial cells (mTECs) is essential for central tolerance. Remarkably, the expression of individual TRAs varies among mTECs and is confined to a perplexingly small number of cells. To reconcile this with the ensuing robust state of tolerance, one might envisage that mTECs serve primarily as an antigen reservoir, whereas tolerogenic recognition of TRAs would ultimately require antigen uptake and presentation by dendritic cells (DCs). Here, we survey the evidence for this 'antigen-spreading' scenario and relate it to findings that document autonomous antigen-presentation by mTECs. We suggest that DC-dependent and autonomous tolerogenic functions of mTECs operate in parallel, and the underlying mechanisms remain to be established.
authors.affiliation: University of Munich, Institute for Immunology, Goethestr. 31, 80336 Munich, Germany. ludger.klein@med.uni-muenchen.de
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein
authors.forename: Maria
authors.initials: M
authors.lastname: Hinterberger
authors.forename: Julia
authors.initials: J
authors.lastname: von Rohrscheidt
authors.forename: Martin
authors.initials: M
authors.lastname: Aichinger
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000276:immunology*
chemical_list: D001324:Autoantigens