Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance
Date
2011
Authors
Hubert, Francois-Xavier
Kinkel, Sarah A
Davey, Gayle M
Phipson, Belinda
Mueller, Scott N
Liston, Adrian
Proietto, Anna
Cannon, Ping Z
Forehan, Simon
Smyth, Gordon K.
Journal Title
Journal ISSN
Volume Title
Publisher
American Society of Hematology
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 OVAunder 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.
Description
Keywords
Keywords: antigen; insulin; ovalbumin; animal experiment; animal tissue; antigen presenting cell; article; CD4+ T lymphocyte; CD8+ T lymphocyte; controlled study; dendritic cell; epithelium cell; human; mouse; nonhuman; priority journal; promoter region; protein ex
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Source
Blood
Type
Journal article
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2037-12-31