佐藤　加代子
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position  
Article types Original article
Language English
Peer review Peer reviewed
Title T cell recognition and killing of vascular smooth muscle cells in acute coronary syndrome.
Journal Formal name：Circulation research
Abbreviation：Circ Res
ISSN code：15244571/00097330
Domestic / ForeginForegin
Publisher American Heart Association
Volume, Issue, Page 98(9),pp.1168-1176
Author and coauthor Pryshchep Sergey†, Sato Kayoko, Goronzy Jörg J, Weyand Cornelia M
Publication date 2006/05
Summary 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.
DOI 10.1161/01.RES.0000220649.10013.5c
PMID 16601227