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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

TOX provides a link between calcineurin activation and CD8 lineage commitment.

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.[1]


  1. TOX provides a link between calcineurin activation and CD8 lineage commitment. Aliahmad, P., O'Flaherty, E., Han, P., Goularte, O.D., Wilkinson, B., Satake, M., Molkentin, J.D., Kaye, J. J. Exp. Med. (2004) [Pubmed]
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