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Circulation Research. 2006;98:1168-1176
Published online before print April 6, 2006, doi: 10.1161/01.RES.0000220649.10013.5c
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(Circulation Research. 2006;98:1168.)
© 2006 American Heart Association, Inc.

Cellular Biology

T Cell Recognition and Killing of Vascular Smooth Muscle Cells in Acute Coronary Syndrome

Sergey Pryshchep, Kayoko Sato, Jörg J. Goronzy, Cornelia M. Weyand

From the Department of Medicine, Lowance Center for Human Immunology, Emory University, Atlanta, Ga.

Correspondence to Cornelia M. Weyand, MD, PhD, Lowance Center for Human Immunology, Emory University, 101 Woodruff Circle #1003, Atlanta, GA 30322. E-mail cweyand{at}emory.edu

Loss of vascular smooth muscle cells (VSMCs) has been proposed to destabilize the atherosclerotic plaque and contribute to plaque rupture, superimposed thrombosis, and acute coronary syndromes (ACSs). We examined whether VSMCs are susceptible to T cell–induced apoptosis and found that CD4 T cells are highly effective in establishing cell–cell contact with VSMCs and triggering apoptotic death. Visualization of the T cell–VSMC contact zone on the single-cell level revealed that both patient-derived and control CD4 T cells reorganized their cell membrane to assemble an immunologic synapse with the VSMCs. Within 4 to 10 minutes, the membrane proximal signaling molecule ZAP-70 was recruited and phosphorylated. However, only patient-derived CD4 T cells sustained an intact immunologic synapse beyond 10 minutes and generated intracellular calcium signals. CD4 T cells that maintained a synaptic contact and appeared to be responsible for VSMC apoptosis accounted for approximately 20% of the circulating memory T cell population in ACS patients and were rare in the blood of age-matched controls. CD4 T cells from ACS patients were also hyperresponsive to T cell receptor–mediated stimulation when triggered by a superantigen and non-VSMC target cells. Lowered setting of the T cell activation threshold, attributable to excessive amplification of proximal CD3-mediated signals, may contribute to CD4 T cell-mediated killing of VSMCs and promote plaque instability.


Key Words: inflammation • lymphocyte • unstable angina • vascular inflammation • vascular smooth muscle cells


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