| First Author | Hubert FX | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 9 | Pages | 2462-72 |
| PubMed ID | 21505196 | Mgi Jnum | J:176949 |
| Mgi Id | MGI:5293219 | Doi | 10.1182/blood-2010-06-286393 |
| Citation | Hubert FX, et al. (2011) Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance. Blood 118(9):2462-72 |
| abstractText | 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. |
