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

Nobuhiko Kayagaki, Noriko Yamaguchi, Masafumi Nakayama, Eto Hiroshi, Ko Okumura, Hideo Yagita

Research output: Contribution to journalArticlepeer-review

410 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1451-1460
Number of pages10
JournalJournal of Experimental Medicine
Volume189
Issue number9
DOIs
Publication statusPublished - 1999 May 3

Keywords

  • Cytotoxic T lymphocyte
  • Cytotoxicity
  • Renal cell carcinoma
  • TRAIL
  • Type I interferon

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this