Immunological tolerance to self is essential for maintaining the integrity of the organ systems, and its breakdown may lead to the development of autoimmune diseases. Tolerance to self is maintained through several mechanisms, which include negative selection, functional inactivation (anergy) and suppression of autoreactive lymphocytes. However, only negative selection permanently removes autoreactive cells through apoptosis. While it has long been known that negative selection requires a T cell receptor (TCR) signal, it is unclear whether a death ligand signal is also involved. TRAIL, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand, is a newly described member of the TNF family. Unlike other death ligands of Immunological tolerance to self is essential for maintaining the integrity of the organ systems, and its breakdown may lead to the development of autoimmune diseases. Tolerance to self is maintained through several mechanisms, which include negative selection, functional inactivation (anergy) and suppression of autoreactive However, only negative selection whether a negative ligand whether or not a death ligand signal is also involved. TRAIL, the tumor necrosis factor (TNF) -related apoptosis-inducing ligand, is newly described member of the TNF family. Unlike other death ligands of