title: Deletional tolerance mediated by extrathymic Aire-expressing cells.
abstract: The prevention of autoimmunity requires the elimination of self-reactive T cells during their development and maturation. The expression of diverse self-antigens by stromal cells in the thymus is essential to this process and depends, in part, on the activity of the autoimmune regulator (Aire) gene. Here we report the identification of extrathymic Aire-expressing cells (eTACs) resident within the secondary lymphoid organs. These stromally derived eTACs express a diverse array of distinct self-antigens and are capable of interacting with and deleting naïve autoreactive T cells. Using two-photon microscopy, we observed stable antigen-specific interactions between eTACs and autoreactive T cells. We propose that such a secondary network of self-antigen-expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection.
authors.affiliation: Diabetes Center, University of California San Francisco (UCSF), San Francisco, CA 94122, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Gardner
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Devoss
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Friedman
authors.forename: David J
authors.initials: DJ
authors.lastname: Wong
authors.forename: Ying X
authors.initials: YX
authors.lastname: Tan
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zhou
authors.forename: Kellsey P
authors.initials: KP
authors.lastname: Johannes
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Su
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000276:immunology; D005786:Gene Expression Regulation; D005952:Glucose-6-Phosphatase / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011506:Proteins / Q000276:immunology; D017634:Self Tolerance; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000096927:AIRE Protein
chemical_list: D001324:Autoantigens; D005952:Glucose-6-Phosphatase; D011506:Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; C117983:G6pc2 protein, mouse