Ablation of TSCOT Expressing Thymic Epithelial Cell Subpopulation Results Early Thymocyte Depletion

초록

Regulated interaction between thymocytes and surrounding stromal cells occurs in the thymus microenvironment during thymopoiesis. Molecules on or by these stromal cells may directly or indirectly regulate genetic programs for thymocyte survival, traffic, selection, and lineage commitment. The gene encoding E. coli nitroreductase (NTR) was specifically expressed in the thymic epithelial cells of the transgenic mice using TSCOT (Thymic Stroma Co-Transporter) promotor. EGFP expression driven by 3.1kb TSCOT promotor appeared limited in the medullary area of the thymus while 9.1kb promoter in the cortical area. Treatment with the prodrugs nirofuration (NFT) and metronidazole (MTZ) resulted in a dose dependant and selective killing of the cells in vitro and in the fetal thymic organ culture system. More detailed analysis of NTR-mediated specific cell ablation in the mouse models will reveal the developmental process and the roles of thymic epithelial cells in the immune system.