| First Author | Aliahmad P | Year | 2004 |
| Journal | J Exp Med | Volume | 199 |
| Issue | 8 | Pages | 1089-99 |
| PubMed ID | 15078895 | Mgi Jnum | J:91035 |
| Mgi Id | MGI:3045816 | Doi | 10.1084/jem.20040051 |
| Citation | Aliahmad P, et al. (2004) TOX Provides a Link Between Calcineurin Activation and CD8 Lineage Commitment. J Exp Med 199(8):1089-99 |
| abstractText | T cell development is dependent on the integration of multiple signaling pathways, although few links between signaling cascades and downstream nuclear factors that play a role in thymocyte differentiation have been identified. We show here that expression of the HMG box protein TOX is sufficient to induce changes in coreceptor gene expression associated with beta-selection, including CD8 gene demethylation. TOX expression is also sufficient to initiate positive selection to the CD8 lineage in the absence of MHC-TCR interactions. TOX-mediated positive selection is associated with up-regulation of Runx3, implicating CD4 silencing in the process. Interestingly, a strong T cell receptor-mediated signal can modify this cell fate. We further demonstrate that up-regulation of TOX in double positive thymocytes is calcineurin dependent, linking this critical signaling pathway to nuclear changes during positive selection. |
