Nature Immunology3, 272 - 280 (2002)
Published online: 19 February 2002; | doi:10.1038/ni767
TOX: an HMG box protein implicated in the regulation of thymocyte selection
Beverley Wilkinson1, Jeff Y.-F. Chen1, 2, Peggy Han1, Kevin M. Rufner1, Olivia D. Goularte1
& Jonathan Kaye1
1
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Present address: Graduate Institutes of Life Sciences, National Defense Medical College, Nei-hu, Taipei, Taiwan.
Correspondence should be addressed to Jonathan Kaye jkaye@scripps.edu
In the thymus, pre-T cell receptor (pre-TCR)−mediated signaling and then TCR-mediated signaling initiate changes in gene expression that result in the maturation of CD4 and CD8 lineage T cells from common precursors. Using gene chip technology, we isolated a murine gene, designated Tox, that encodes a member of the HMG (high-mobility group) box family of DNA-binding proteins. TOX expression is up-regulated by both pre-TCR and TCR activation of immature thymocytes but not by TCR activation of mature naïve T cells. Transgenic mice that express TOX show expanded CD8+ and reduced CD4+ single positive thymocyte subpopulations. We present evidence here that this phenotype results from a perturbation in lineage commitment due to reduced sensitivity to TCR-mediated signaling. This molecular marker of thymic selection events may therefore play a role in establishing the activation threshold of developing T cells and patterning changes in gene expression.
