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TOX provides a link between calcineurin activation and CD8 lineage commitment

Parinaz Aliahmad1, Emmett O'Flaherty, Peggy Han

  • 1Department of Immunology IMM-8, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.

The Journal of Experimental Medicine
|April 14, 2004
PubMed

Insights

The HMG box protein TOX drives T cell development by altering coreceptor gene expression and initiating CD8 lineage selection, independent of typical T cell receptor signals. This process involves Runx3 up-regulation and calcineurin signaling.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • T cell development requires integrating multiple signaling pathways.
  • Few links are known between signaling cascades and nuclear factors in thymocyte differentiation.

Purpose of the Study:

  • To investigate the role of the HMG box protein TOX in T cell development.
  • To identify downstream nuclear factors and signaling pathways involved in thymocyte differentiation.

Main Methods:

  • Assessing the effects of TOX expression on coreceptor gene expression.
  • Analyzing CD8 gene demethylation and CD4 silencing.
  • Investigating the role of calcineurin signaling in TOX up-regulation.

Main Results:

  • TOX expression induces changes in coreceptor gene expression, including CD8 gene demethylation.
  • TOX initiates CD8 lineage positive selection independently of MHC-TCR interactions.
  • TOX up-regulation is calcineurin-dependent and linked to Runx3 up-regulation and CD4 silencing.

Conclusions:

  • TOX is a key nuclear factor in T cell development, influencing coreceptor expression and lineage commitment.
  • Calcineurin signaling is critical for TOX up-regulation during positive selection, linking signaling pathways to nuclear events.
  • TOX plays a significant role in CD8 lineage commitment, with potential implications for understanding T cell differentiation defects.

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