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https://hdl.handle.net/2440/67129
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Type: | Journal article |
Title: | Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance |
Author: | Hubert, F. Kinkel, S. Davey, G. Phipson, B. Mueller, S. Liston, A. Proietto, A. Cannon, P. Forehan, S. Smyth, G. Wu, L. Goodnow, C. Carbone, F. Scott, H. Heath, W. |
Citation: | Blood, 2011; 118(9):2462-2472 |
Publisher: | Amer Soc Hematology |
Issue Date: | 2011 |
ISSN: | 0006-4971 1528-0020 |
Statement of Responsibility: | François-Xavier Hubert, Sarah A. Kinkel, Gayle M. Davey, Belinda Phipson, Scott N. Mueller, Adrian Liston, Anna I. Proietto, Ping Z. F. Cannon, Simon Forehan, Gordon K. Smyth, Li Wu, Christopher C. Goodnow, Francis R. Carbone, Hamish S. Scott and William R. Heath |
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 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 mTECs can mediate tolerance by direct presentation of Aire-regulated antigens to both CD4 and CD8 T cells. |
Keywords: | Thymus Gland Dendritic Cells CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Epithelial Cells Animals Radiation Chimera Mice, Transgenic Mice Insulin Ovalbumin Recombinant Fusion Proteins Transcription Factors Antigens Cytokines Bone Marrow Transplantation Crosses, Genetic Immune Tolerance Clonal Deletion Antigen Presentation Gene Expression Regulation Promoter Regions, Genetic |
Rights: | © 2011 by The American Society of Hematology |
DOI: | 10.1182/blood-2010-06-286393 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/171601 http://purl.org/au-research/grants/nhmrc/461202 http://purl.org/au-research/grants/nhmrc/461204 http://purl.org/au-research/grants/nhmrc/257501 http://purl.org/au-research/grants/nhmrc/264573 http://purl.org/au-research/grants/nhmrc/406700 http://purl.org/au-research/grants/nhmrc/454465 |
Published version: | http://dx.doi.org/10.1182/blood-2010-06-286393 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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