A DOMINANT INTERFERING MUTANT OF FADD MORT1 ENHANCES DELETION OF AUTOREACTIVE THYMOCYTES AND INHIBITS PROLIFERATION OF MATURE T-LYMPHOCYTES/

Members of the tumour necrosis factor receptor family that contain a d eath domain have pleiotropic activities. They induce apoptosis via int eraction with intracellular FADD/MORT1 and trigger cell growth or diff erentiation via TRADD and TRAF molecules. The impact of FADD/MORT1-tra nsduced signals on T lymphocyte development was investigated in transg enic mice expressing a dominant negative mutant protein, FADD-DN, Unex pectedly, FADD-DN enhanced negative selection of self-reactive thymic lymphocytes and inhibited T cell activation by increasing apoptosis, T hus signalling through FADD/MORT1 does not lead exclusively to cell de ath, but under certain circumstances can promote cell survival and pro liferation.