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Status |
Public on Apr 06, 2011 |
Title |
Aire regulates transfer of antigen from mTEC to dendritic cells for induction of thymic tolerance |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
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.
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Overall design |
Total RNA was extracted from medullary thymic epithelial cells isolated from wildtype and Aire-deficient C57BL/6 mice for comparison of gene expression profiles.
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Contributor(s) |
Hubert F, Kinkel SA, Davey GM, Phipson B, Mueller SN, Liston A, Proietto AI, Cannon PZ, Forehan S, Smyth GK, Wu L, Goodnow CC, Carbone FR, Scott HS, Heath WR |
Citation(s) |
21505196 |
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Submission date |
Apr 05, 2011 |
Last update date |
Mar 23, 2012 |
Contact name |
Francois-Xavier Hubert |
E-mail(s) |
hubert@wehi.edu.au
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Organization name |
The Walter and Eliza Hall Institute of Medical Research
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Department |
Immunology
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Street address |
1G Royal Parade
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City |
Melbourne |
State/province |
Victoria |
ZIP/Postal code |
3052 |
Country |
Australia |
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Platforms (1) |
GPL6481 |
Illumina mouse-6 v1.1 expression beadchip [Array_Address_Id version] |
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Samples (6)
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Relations |
BioProject |
PRJNA139083 |
Supplementary file |
Size |
Download |
File type/resource |
GSE28393_full_normalized_matrix.txt.gz |
2.1 Mb |
(ftp)(http) |
TXT |
GSE28393_non-normalized.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
Processed data are available on Series record |
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