Type I interferons (IFNs) regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on human T cells: A novel mechanism forthe antitumor effects of type IIFNs

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a proapoptotic member of the TNF family of type II membrane proteins, which c onstitutes one component of T cell cytotoxicity. In this study, we investig ated the expression and function of TRAIL in human peripheral blood T (PBT) cells. Although freshly isolated PET cells did not express a detectable le vel of TRAIL on their surface, a remarkable TRAIL expression was rapidly in duced on the surface of both CD4(+) and CD8(+) PET cells upon stimulation w ith anti-CD3 monoclonal antibody and type I interferons (IFNs). This enhanc ement of TRAIL expression was a unique feature of type I IFNs (IFN-alpha an d IFN-beta), and neither type II IFN (IFN-gamma) nor various other cytokine s enhanced TRAIL expression on anti-CD3-stimulated PET cells. Type I IFNs h ave been used for clinical treatment of renal cell carcinomas (RCCs), and w e found that most RCC cell lines were susceptible to TRAIL-induced apoptosi s. Type I IFNs substantially augmented cytotoxic activity of anti-CD3-stimu lated PET cells against RCC cell lines in a TRAIL-dependent manner. These r esults indicate a unique feature of type I IFNs to regulate TRAIL-mediated T cell cytotoxicity, which may be involved in the antitumor effects of type I IFNs against various tumors.