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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2305.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Expansion of T-Cell Receptor ^dim Effector T Cells in Acute Coronary Syndromes

Enrico Ammirati; Anna-Chiara Vermi; Domenico Cianflone; Michela Banfi; Chiara Foglieni; Cosmo Godino; Flavio Airoldi; Luca A. Ferri; Claire L. Gorman; Angelo A. Manfredi; Attilio Maseri; Andrew P. Cope; Claudia Monaco

From the Clinical Cardiovascular Biology Research Centre (E.A., A.C.V., M.B., C.F., A.M.) and Clinical Immunology (A.A.M.), Vita-Salute San Raffaele University and San Raffaele Scientific Institute; the Coronary Care Unit (D.C., L.A.F.) and Invasive Cardiology Unit (C.G., F.A.), San Raffaele Scientific Institute, Milan, Italy; and the Kennedy Institute of Rheumatology Division (C.L.G., A.P.C., C.M.), Faculty of Medicine, Imperial College London, UK.

Correspondence to Enrico Ammirati, MD, Clinical Cardiovascular Biology Research Centre, Vita-Salute San Raffaele University and San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy. E-mail ammirati.enrico{at}hsr.it and Claudia Monaco, MD, PhD, Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, 65 Aspenlea Rd. W6 8LH London, UK. E-mail c.monaco@imperial.ac.uk

Objective— The T-cell receptor zeta (TCR)-chain is a master sensor and regulator of lymphocyte responses. Loss of TCR-chain expression has been documented during infectious and inflammatory diseases and defines a population of effector T cells (TCR^dim T cells) that migrate to inflamed tissues. We assessed the expression and functional correlates of circulating TCR^dim T cells in coronary artery disease.

Methods and Results— We examined the expression of TCR-chain by flow cytometry in 140 subjects. Increased peripheral blood CD4⁺ TCR^dim T cells were found in patients with acute coronary syndromes (ACS, n=66; median 5.3%, interquartile 2.6 to 9.1% of total CD4⁺ T cells; P<0.0001) compared to chronic stable angina (CSA, n=32; 1.6%; 1.0 to 4.1%) and controls (n=42; 1.5%; 0.5 to 2.9%). Such increase was significantly greater in ACS patients with elevated levels of C-reactive protein, and it persisted after the acute event. Moreover, TCR^dim cells were also more represented within CD8⁺ T cell, NK, and CD4⁺CD28^null T cell subsets in ACS compared to CSA and controls. Finally, CD4⁺ and CD8⁺ TCR^dim T cells isolated from ACS displayed an enhanced transendothelial migratory capacity.

Conclusions— TCR^dim T cells, an effector T-cell subset with transendothelial migratory ability, are increased in ACS, and may be implicated in coronary instability.

Reduction of TCR-chain expression defines antigen-experienced effector T cells (TCR^dim T-cells) described in inflammatory and infectious diseases. We found increased numbers of TCR^Dim T cells in patients with acute coronary syndromes compared to stable angina and controls, with enhanced transendothelial migratory ability, which may be implicated in the pathogenesis of coronary instability.

Key Words: acute coronary syndrome • lymphocytes • flow cytometry • immune system • receptors