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See Latest ArticlesAltered Thymic Selection and Increased Autoimmunity Caused by Ectopic Expression of DRAK2 during T Cell Development
Journal of Immunology, 06/23/09
Gatzka M et al. - These findings suggest that alteration in thymocyte signaling thresholds impacts the sensitivity of peripheral T cell pools.
Dr. Craig M. Walsh, 06/23/09
| In this work, we ectopically expressed the serine/threonine kinase DRAK2 in thymocytes. In previous work, we have established that DRAK2 negatively regulates T cell activation in peripheral T cells and late thymocyte populations. Here, we demonstrate that expression of DRAK2 in the double-positive stage, where it is normally expressed only at very low levels, diminishes thymocyte selection. This is likely due to the artificially high activation barrier imposed by DRAK2. The surprising result is that peripheral T cells obtained from these mice have a reduced activation threshold compared to wildtype T cells (and the transgenic DRAK2 is not expressed in these peripheral cells). Our findings suggest that imposition of a high signaling threshold during thymocyte selection leads to the development of peripheral T cells with enhanced T cell antigen receptor (TCR)signaling properties. These studies underscore the concept that any T cell therapies directed toward manipulating TCR signaling should take into account potential effects during T cell development in the thymus. |
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