Specific epithelila requirement for gamma delta T cell development revealed in the cell ablation Transgenic System with TSCOT Promoter

초록

To investigate the role of thymic epithelial cells during T-cell development, we used two inducible cell-specific ablation systems with nitroreductase and EGFP genes. Two different lengths of the TSCOT promoter in transgenic mice, 3.1T-NE and 9.1T-NE, drive EGFP expression into TEC specific fashion. In adult life, EGFP expression was located in the medulla with 3.1kb TSCOT promoter, while it was maintained in the cortex with 9.1kb, suggesting the presence of compartment specific cis elements. Nitroreductase induced cell death was specific without bystander killing and the dose dependent of prodrug in cell culture and fetal thymic organ cultures. Fetal thymic stromal cells were analyzed based on the expression levels of EpCAM, MHCII, CDR1 and/or UEA-1. CD4+CD8+ DP cells were highly susceptible to prodrugs in both lines. Surprisingly, there was a distinct reduction in γδT cell population only in the 9.1T-NE, indicating that they require NTR-EGFP expressing TEC population. Therefore, these results support a division of labor within TEC subsets for the αβ and γδ lineage specification. (This work was supported by the Mid Career Grant from NRF)