TY - JOUR
T1 - Type I interferons (IFNs) regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on human T cells
T2 - A novel mechanism for the antitumor effects of type I IFNs
AU - Kayagaki, Nobuhiko
AU - Yamaguchi, Noriko
AU - Nakayama, Masafumi
AU - Hiroshi, Eto
AU - Okumura, Ko
AU - Yagita, Hideo
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/5/3
Y1 - 1999/5/3
N2 - 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-α and IFN-β), and neither type II IFN (IFN-γ) 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.
AB - 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-α and IFN-β), and neither type II IFN (IFN-γ) 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.
KW - Cytotoxic T lymphocyte
KW - Cytotoxicity
KW - Renal cell carcinoma
KW - TRAIL
KW - Type I interferon
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U2 - 10.1084/jem.189.9.1451
DO - 10.1084/jem.189.9.1451
M3 - Article
C2 - 10224285
AN - SCOPUS:0033519303
VL - 189
SP - 1451
EP - 1460
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 9
ER -