Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
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-3Ralpha(+) 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.
Fanger
N A
NA
Department of Discovery Research, Immunex Corporation, Seattle, Washington 98101, USA.
Maliszewski
C R
CR
Schooley
K
K
Griffith
T S
TS
D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D006651:Histocytochemistry; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000276:immunology; D007372:Interferons / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D016167:Integrin alphaXbeta2; D008562:Membrane Glycoproteins; D016185:Receptors, Interleukin-3; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons