CUTTING EDGE - LYMPHOCYTE INHIBITOR OF TRAIL (TNF-RELATED APOPTOSIS-INDUCING LIGAND) - A NEW RECEPTOR PROTECTING LYMPHOCYTES FROM THE DEATHLIGAND TRAIL

Apoptosis can be triggered by the engagement of cell surface receptors by their ligands. A growing number of receptors belonging to the TNF receptor family have been identified that contain a conserved cytoplas mic death domain. These include Fas, TNF-R1, lymphocyte-associated rec eptor of death (LARD), DR4, and TNF-related apoptosis-inducing ligand receptor inducer of cell killing-2 (TRICK2). The latter two are recept ors for the cytotoxic ligand TNF-related apoptosis-inducing ligand (TR AIL), and one of the paradoxes raised by the cloning of these molecule s was why do most cells not die upon contact with the widely expressed TRAIL molecule? This is a particular problem for lymphocytes that exp ress DR4 and TRICK2. and are in constant circulation through TRAIL-exp ressing tissues. We have cloned LIT (lymphocyte inhibitor of TRAIL), w hich lacks a death domain. LIT is expressed predominantly on PBL, wher e it can competitively inhibit TRAIL-induced apoptosis through DR4/TRI CK2, and may function to modulate lymphocyte sensitivity to TRAIL.