| First Author | Gray D | Year | 2007 |
| Journal | J Exp Med | Volume | 204 |
| Issue | 11 | Pages | 2521-8 |
| PubMed ID | 17908938 | Mgi Jnum | J:126040 |
| Mgi Id | MGI:3760446 | Doi | 10.1084/jem.20070795 |
| Citation | Gray D, et al. (2007) Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med 204(11):2521-8 |
| abstractText | Expression of autoimmune regulator (Aire) by thymic medullary epithelial cells (MECs) is critical for central tolerance of self. To explore the mechanism by which such a rare cell population imposes tolerance on the large repertoire of differentiating thymocytes, we examined the proliferation and turnover of Aire(+) and Aire(-) MEC subsets through flow cytometric analysis of 5-bromo-2'deoxyuridine (BrdU) incorporation. The Aire(+) MEC subset was almost entirely postmitotic and derived from cycling Aire(-) precursors. Experiments using reaggregate thymic organ cultures revealed the presence of such precursors among Aire(-) MECs expressing low levels of major histocompatibility complex class II and CD80. The kinetics of BrdU decay showed the Aire(+) population to have a high turnover. Aire did not have a direct impact on the division of MECs in vitro or in vivo but, rather, induced their apoptosis. We argue that these properties strongly favor a 'terminal differentiation' model for Aire function in MECs, placing strict temporal limits on the operation of any individual Aire(+) MEC in central tolerance induction. We further speculate that the speedy apoptosis of Aire-expressing MECs may be a mechanism to promote cross-presentation of the array of peripheral-tissue antigens they produce. |
