In the immune system, developing thymocytes depend critically on an intimate association with the organized stromal microenvironment of the thymus, which is made up primarily of thymic epithelial cells. Akiyama et al. demonstrate the importance of this association for T cell tolerance. A deficiency in the RING domain ubiquitin ligase TRAF6 caused a loss of organized thymic epithelial architecture. The severe impairment of T cell development then leads to autoimmunity.
T. Akiyama, S. Maeda, S. Yamane, K. Ogino, M. Kasai, F. Kajiura, M. Matsumoto, J.-I. Inoue, Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science 308, 248-251 (2005). [Abstract] [Full Text]