TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque

Kayoko Sato, Alexander Niessner, Stephen L. Kopecky, Robert L. Frye, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

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 apoptosisinducing 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. JEM

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalJournal of Experimental Medicine
Volume203
Issue number1
DOIs
StatePublished - Jan 23 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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