TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque.
Acute coronary syndromes (ACS) are precipitated by a rupture of the atherosclerotic plaque, often at the site of T cell and macrophage infiltration. Here, we show that plaque-infiltrating CD4 T cells effectively kill vascular smooth muscle cells (VSMC). VSMCs sensitive to T cell-mediated killing express the death receptor DR5 (TNF-related apoptosis-inducing ligand [TRAIL] receptor 2), and anti-TRAIL and anti-DR5 antibodies block T cell-mediated apoptosis. CD4 T cells that express TRAIL upon stimulation are expanded in patients with ACS and more effectively induce VSMC apoptosis. Adoptive transfer of plaque-derived CD4 T cells into immunodeficient mice that are engrafted with human atherosclerotic plaque results in apoptosis of VSMCs, which was prevented by coadministration of anti-TRAIL antibody. These data identify that the death pathway is triggered by TRAIL-producing CD4 T cells as a direct mechanism of VSMC apoptosis, a process which may lead to plaque destabilization.
Sato
Kayoko
K
Department of Medicine, Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory School of Medicine, Atlanta, GA 30322, USA.
Niessner
Alexander
A
Kopecky
Stephen L
SL
Frye
Robert L
RL
Goronzy
Jörg J
JJ
Weyand
Cornelia M
CM
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002339:Carotid Arteries; D002460:Cell Line; D002478:Cells, Cultured; D006331:Heart Diseases / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D016378:Tissue Transplantation; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha