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(Circulation. 2006;113:640-646.)
© 2006 American Heart Association, Inc.

Coronary Heart Disease

Patients With Acute Coronary Syndrome Show Oligoclonal T-Cell Recruitment Within Unstable Plaque

Evidence for a Local, Intracoronary Immunologic Mechanism

Raffaele De Palma, MD, PhD; Francesco Del Galdo, MD; Gianfranco Abbate, MD; Massimo Chiariello, MD; Raffaele Calabró, MD; Lavinia Forte, MD; Giovanni Cimmino, MD; Maria Francesca Papa, BSc; Maria Giovanna Russo, MD; Giuseppe Ambrosio, MD, PhD; Claudio Giombolini, MD; Isabella Tritto, MD; Salvatore Notaristefano, MD; Liberato Berrino, MD; Francesco Rossi, MD; Paolo Golino, MD, PhD

From the Department of Clinical and Experimental Medicine (R.D.P., F.D.G., G.A., M.F.P.), Department of Experimental Medicine, Section of Pharmacology (L.B., F.R.), and Department of Cardiothoracic and Respiratory Sciences, Section of Cardiology (R.C., L.F., G.C., M.G.R., P.G.), Second University of Naples, Naples; Department of Internal Medicine and Cardiovascular Sciences (M.C.), Division of Cardiology, University of Naples "Federico II", Naples; and the Division of Cardiology (G.A., C.G., I.T., S.N.), University of Perugia, Perugia, Italy.

Correspondence to Paolo Golino, MD, PhD, Division of Cardiology, Second University of Naples, Ospedale Monaldi, Via Leonardo Bianchi, 80131 Naples, Italy. E-mail paolo.golino{at}unina2.it

Received January 21, 2005; revision received September 28, 2005; accepted November 22, 2005.

Background— Recent studies indicate that T-cell activation may play an important role in the pathophysiology of acute coronary syndromes (ACS). However, although those studies detected T-cell expansion in peripheral blood cells, demonstration of specific T-cell expansion within the plaque of patients with ACS is lacking. The present study aims to address whether a specific, immune-driven T-lymphocyte recruitment occurs within the unstable plaque of patients with ACS.

Methods and Results— We simultaneously examined the T-cell repertoire using CDR3 size analysis both in coronary plaques (obtained by directional atherectomy) and in peripheral blood of patients with either ACS (n=11) or chronic stable angina (n=10). Unstable plaques showed a 10-fold increase in T-cell content by quantitative PCR. Using spectratyping analysis, we found several specific T-cell clonotype expansions only in unstable plaque from each patient with ACS, indicating a specific, antigen-driven recruitment of T cells within unstable lesions.

Conclusions— For the first time, T-cell repertoire was investigated directly into coronary plaques; using this approach, we demonstrate that coronary plaque instability in the setting of ACS is associated with immune-driven T-cell recruitment, specifically within the plaque.

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