Dataset Information


Aire regulates transfer of antigen from mTEC to dendritic cells for induction of thymic tolerance

ABSTRACT: To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter (RIP). Aire-deficiency reduced the number of mature single positive (SP) OVA-specific CD4+ or CD8+ T cells in the thymus, independent of OVA expression. Importantly, it also contributed in two way to OVA-dependent negative selection depending on the T cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to mTEC-expressed OVA. This study supports the view that one mechanism by which Aire controls thymic negative selection is by regulating the indirect presentation of mTEC-derived antigens by thymic dendritic cells. It also indicates that mTEC can mediate tolerance by direct presentation of Aireregulated antigens to both CD4 and CD8 T cells. Total RNA was extracted from medullary thymic epithelial cells isolated from wildtype and Aire-deficient C57BL/6 mice for comparison of gene expression profiles.

ORGANISM(S): Mus musculus  

SUBMITTER: William R Heath   Anna I Proietto  Sarah A Kinkel  Francis R Carbone  Gordon K Smyth  Ping Z Cannon  Adrian Liston  Hamish S Scott  Gayle M Davey  Christopher C Goodnow  Scott N Mueller  Belinda Phipson  Francois-Xavier Hubert  Simon Forehan  Li Wu 

PROVIDER: E-GEOD-28393 | ArrayExpress | 2011-04-06



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