J. Exp. Med., Volume 189, Number 9, May 3, 1999 1451-1460
Type I Interferons (IFNs) Regulate Tumor Necrosis
Factor-related Apoptosis-inducing Ligand
(TRAIL) Expression on Human T Cells: A Novel
Mechanism for the Antitumor Effects of Type I IFNs
By Nobuhiko Kayagaki,* Noriko Yamaguchi,* Masafumi Nakayama,* Hiroshi Eto,§ Ko Okumura,* and Hideo
Yagita*
From the * Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan; Core
Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Chiyoda-ku,
Tokyo 101-0062, Japan; and the § Department of Urology, Kobe University School of Medicine, Chuo-ku, Hyogo
650-0017, Japan
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a proapoptotic member of the TNF family of type
II membrane proteins, which constitutes one component of T cell cytotoxicity. In this study, we investigated the expression and
function of TRAIL in human peripheral blood T (PBT) cells. Although freshly isolated PBT cells did not express a detectable
level of TRAIL on their surface, a remarkable TRAIL expression was rapidly induced on the surface of both CD4+ and CD8+
PBT cells upon stimulation with anti-CD3 monoclonal antibody and type I interferons (IFNs). This enhancement of TRAIL
expression was a unique feature of type I IFNs (IFN- and IFN-), and neither type II IFN (IFN-) nor various other
cytokines enhanced TRAIL expression on anti-CD3-stimulated PBT cells. Type I IFNs have been used for clinical treatment of
renal cell carcinomas (RCCs), and we found that most RCC cell lines were susceptible to TRAIL-induced apoptosis. Type I
IFNs substantially augmented cytotoxic activity of anti-CD3-stimulated PBT cells against RCC cell lines in a TRAIL-dependent
manner. These results 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. |
