Our data show that RB plays a critical role on controlling thymus size by suppressing TECs proliferation cell-autonomously, and also thymocytes proliferation cell non-autonomously. T cell differentiation and maturation were not affected by RB-TS inactivation in TECs, suggesting that RB-TS inactivation in TECs is not sufficient to disrupt T cell development. Thus, it is very attempting to manipulate TECs as a therapeutic strategy in order to enhance the immune function in a wide variety of patients. However, long term inactivating RB-TS in TECs will have detrimental effect on animals. We have finished this project and are currently in the process of preparing the manuscript for publication. Y. Song, T.Sullivan, K.Klarmann, D.Gilbert, T. N. O'Sullivan, L.Lu, D.C. Haines, J. Keller, and T. Van Dyke. Inactivation of RB in thymic cytokeratin 18 cells results in lymphoid and stromal proliferative disorder in genetically engineered mice (in preparation)