T-CELL RECEPTOR-DEPENDENT CELL-DEATH OF T-CELL HYBRIDOMAS MEDIATED BYTHE CD30 CYTOPLASMIC DOMAIN IN ASSOCIATION WITH TUMOR-NECROSIS-FACTORRECEPTOR-ASSOCIATED FACTORS

CD30 is a member of the tumor necrosis factor receptor superfamily and a surface marker for Hodgkin's disease. Normal activated T cells and several virally transformed T or B cell lines also show CD30 expressio n. The interaction of CD30 with its ligand induces cell death or proli feration, depending on the cell type. In this report we characterize t he signals mediated by the intracellular domain of CD30 and show that, in combination with signal(s) transduced by the T cell receptor, the multimerization of CD30 cytoplasmic domain induces Fas(CD95)-independe nt cell death in T cell hybridomas. Deletion analysis shows that the C OOH-terminal 66 amino acids of CD30 are required to induce cell death. Using the yeast two-hybrid system, we have identified that the same r egion of CD30 interacts with tumor necrosis factor receptor-associated factor (TRAF)1 and TRAF2. These results indicate that TRAF1 and/or TR AF2 play an important role in cell death in addition to their previous ly identified roles in cell proliferation.