TRAIL/Apo-2-ligand-induced apoptosis in human T cells

Abstract

Members of the tumor necrosis factor (TNF) family such as CD95 (APO‐1/Fas) ligand (L) trigger apoptosis in lymphoid cells. Recently, a new member of apoptosis‐inducing ligands, TRAIL (TNF‐related‐apoptosis‐inducing‐ligand)/Apo‐2 ligand, was identified that might act in a similar way. We compared TRAIL and CD95L‐induced apoptosis in human lymphoid cells. Expression of TRAIL was found in CD4+ and CD8+ T cells following activation, suggesting that TRAIL participates in T cell‐mediated induction of apoptosis. Similar to CD95L, TRAIL‐induced apoptosis in target cells is mediated by activation of caspases (ICE/Ced‐3 proteases). However, different human lymphoid cell lines and peripheral T cells differ in sensitivity towards induction of apoptosis by TRAIL and CD95L. In addition, T cells are highly sensitive towards CD95L‐induced apoptosis after prolonged activation in vitro, but remain completely resistant to TRAIL‐induced apoptosis. In contrast, T cells from HIV‐1‐infected patients previously shown to exhibit increased CD95 sensitivity are even more susceptible towards TRAIL‐induced cell death. These data suggest that TRAIL might participate in CD95‐independent apoptosis of lymphoid cells and might be involved in deregulated apoptosis in diseases such as leukemias and HIV‐1 infection.