Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Neil A. Fanger, Charles R. Maliszewski, Ken Schooley, Thomas S. Griffith

Research output: Contribution to journalArticle

328 Scopus citations

Abstract

TRAIL (TNF-related apoptosis-inducing ligand) is a member of the TNF family that induces apoptosis in a variety of cancer cells. In this study, we demonstrate that human CD11c+ blood dendritic cells (DCs) express TRAIL after stimulation with either interferon (IFN)-γ or -α and acquire the ability to kill TRAIL-sensitive tumor cell targets but not TRAIL-resistant tumor cells or normal cell types. The DC-mediated apoptosis was TRAIL specific, as soluble TRAIL receptor blocked target cell death. Moreover, IFN- stimulated interleukin (IL)-3 receptor (R)α+ blood precursor (pre-)DCs displayed minimal cytotoxicity toward the same target cells, demonstrating a clear functional difference between the CD11c+ DC and IL-3Rα+ pre-DC subsets. These results indicate that TRAIL may serve as an innate effector molecule on CD11c+ DCs for the elimination of spontaneously arising tumor cells and suggest a means by which TRAIL-expressing DCs may regulate or eliminate T cells responding to antigen presented by the DCs.

Original languageEnglish (US)
Pages (from-to)1155-1164
Number of pages10
JournalJournal of Experimental Medicine
Volume190
Issue number8
DOIs
StatePublished - Oct 18 1999

Keywords

  • Apoptosis
  • Dendritic cells
  • Human
  • TRAIL
  • Tumor

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