Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance
- Author(s)
- Hubert, FX; Kinkel, SA; Davey, GM; Phipson, B; Mueller, SN; Liston, A; Proietto, AI; Cannon, PZF; Forehan, S; Smyth, GK; Wu, L; Goodnow, CC; Carbone, FR; Scott, HS; Heath, WR;
- Details
- Publication Year 2011-09-01,Volume 118,Issue #9,Page 2462-2472
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- 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. Aire deficiency reduced the number of mature single-positive OVA-specific CD4(+) or CD8(+) T cells in the thymus, independent of OVA expression. Importantly, it also contributed in 2 ways 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 medullary thymic epithelial cell (mTEC)-expressed OVA. This study supports the
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- T-CELLS; EPITHELIAL-CELLS; SELF-TOLERANCE; ILLUMINA MICROARRAY; AUTOIMMUNE-DISEASE; INSULIN EXPRESSION; DEFICIENT MICE; IDDM2 LOCUS; GENE; SELECTION
- Publisher's Version
- https://doi.org/10.1182/blood-2010-06-286393
- Open Access at Publisher's Site
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Creation Date: 2011-09-01 12:00:00