TOX Provides a Link between Calcineurin Activation and CD8 Lineage Commitment

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

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)1089-1099
Number of pages11
JournalJournal of Experimental Medicine
Volume199
Issue number8
DOIs
Publication statusPublished - 2004 Apr 19

Keywords

  • Gene regulation
  • HMG box
  • Runx
  • T cell development
  • TCR signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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