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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
Statement of
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
Radiation Chimera
Mice, Transgenic
Recombinant Fusion Proteins
Transcription Factors
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
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Published version:
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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