Details

Autor(en) / Beteiligte

• Aliahmad, Parinaz
• O'Flaherty, Emmett
• Han, Peggy
• Goularte, Olivia D
• Wilkinson, Beverley
• Satake, Masanobu
• Molkentin, Jeffery D
• Kaye, Jonathan

Titel

TOX provides a link between calcineurin activation and CD8 lineage commitment

Ist Teil von

• The Journal of experimental medicine, 2004-04, Vol.199 (8), p.1089-1099

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.