THE FAS-DEFICIENT SCID MOUSE EXHIBITS THE DEVELOPMENT OF T-CELLS IN THE THYMUS

The Fas Ag is a cell surface protein that mediates apoptosis and is hi ghly expressed on thymocytes. However, the role of the Fas system in t he thymus is unclear, To study the role of the Fas system in the thymu s, we established a novel SCID mouse bearing the lpr (lymphoproliferat ion) mutation. Thymocytes from these mice differentiated into CD4(+)CD 8(+) T cells and then underwent further differentiation into CD4(+)CD8 (-) or CD4(-)CD8(+) single-positive T cells with a low surface express ion of CD3, whereas B cell development remained unrescued. These TCR-p ositive T cells can proliferate in response to stimulation with PMA pl us ionomycin, but not with third-party spleen cells. Furthermore, thym ocytes from scid/lpr mice had a great variety of TCR V beta repertoire s, These results suggest that the Fas system plays an essential role i n regulating the development of intrathymic T cells as well as periphe ral T cells.