Expression and function of TNF-related apoptosis-inducing ligand on murineactivated NK cells

TNF-related apoptosis-inducing ligand (TRAIL), a new member of TNF family, induces apoptotic cell death of various tumor cells. We recently showed tha t TRAIL mediates perforin- and Pas ligand (FasL)-independent cytotoxic acti vity of human CD4(+) T cell clones. In the present study, we investigated t he expression and function of TRAIL on murine lymphocytes by using newly ge nerated anti-murine TRAIL mAbs, Although freshly isolated T, B, or NK cells did not express a detectable level of TRAIL on their surface, a remarkable level of TRAIL expression was induced preferentially on CD3(-) NK1.1(+) NK cells after stimulation with IL-2 or IL-15. In contrast, TRAIL expression was not induced by IL-18, whereas it efficiently potentiated lymphokine-act ivated killer activity of NK cells. In addition to perforin inactivation an d neutralization of FasL by anti-FasL mAb, neutralization of TRAIL by anti- TRAIL mAb was needed for the complete inhibition of IL-2- of IL-15-activate d NIC cell cytotoxicity against mouse fibrosarcoma L929 target cells, which were susceptible to both Fast and TRAIL. These results indicated preferent ial expression of TRAIL on IL-2- or IL-15-activated NK cells and its potent ial involvement in lymphokine-activated killer activity.