The Fas Ag is a cell surface protein that mediates apoptosis and is highly expressed on thymocytes. However, the role of the Fas system in the thymus is unclear. To study the role of the Fas system in the thymus, we established a novel SCID mouse bearing the lpr (lymphoproliferation) mutation. Thymocytes from these mice differentiated into CD4+ CD8+ T cells and then underwent further differentiation into CD4+ CD8- or CD4- CD8+ single-positive T cells with a low surface expression of CD3, whereas B cell development remained unrescued. These TCR-positive T cells can proliferate in response to stimulation with PMA plus ionomycin, but not with third-party spleen cells. Furthermore, thymocytes from scid/lpr mice had a great variety of TCR Vbeta repertoires. These results suggest that the Fas system plays an essential role in regulating the development of intrathymic T cells as well as peripheral T cells.

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