The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1999/10/1155/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 8, October 18, 1999 1155-1164

Original Article

Human Dendritic Cells Mediate Cellular Apoptosis via Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail)

Neil A. Fangera, Charles R. Maliszewskia, Ken Schooleyb, and Thomas S. Griffithc

a Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101
b Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101
c Department of Immunobiology, Immunex Corporation, Seattle, Washington 98101
Dept. of Urology, 428 MRC, University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242-1089.319-356-3900319-335-7581

griffitht{at}mail.medicine.uiowa.edu

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)-{gamma} or -{alpha} 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){alpha}+ blood precursor (pre-)DCs displayed minimal cytotoxicity toward the same target cells, demonstrating a clear functional difference between the CD11c+ DC and IL-3R{alpha}+ 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.

Key Words: TRAIL • apoptosis • tumor • dendritic cells • human

1used in this paper: DCs, dendritic cells; FLIP, FLICE (Fas-associated death domain–like IL-1β–converting enzyme)-inhibitory protein; L, ligand; LZ, leucine zipper; M{varphi}, monocytes; RT, reverse transcriptase; TRAIL, TNF-related apoptosis-inducing ligand

© 1999 The Rockefeller University Press


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