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OBJECTIVE: The T-cell receptor zeta (TCR zeta)-chain is a master sensor and regulator of lymphocyte responses. Loss of TCR zeta-chain expression has been documented during infectious and inflammatory diseases and defines a population of effector T cells (TCR zeta(dim) T cells) that migrate to inflamed tissues. We assessed the expression and functional correlates of circulating TCR zeta(dim) T cells in coronary artery disease. METHODS AND RESULTS: We examined the expression of TCR zeta-chain by flow cytometry in 140 subjects. Increased peripheral blood CD4(+) TCR zeta(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 zeta(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 zeta(dim) T cells isolated from ACS displayed an enhanced transendothelial migratory capacity. CONCLUSIONS: TCR zeta(dim) T cells, an effector T-cell subset with transendothelial migratory ability, are increased in ACS, and may be implicated in coronary instability.

Original publication

DOI

10.1161/ATVBAHA.108.174144

Type

Journal article

Journal

Arterioscler Thromb Vasc Biol

Publication Date

12/2008

Volume

28

Pages

2305 - 2311

Keywords

Acute Coronary Syndrome, Adult, Aged, Angina Pectoris, Atherosclerosis, C-Reactive Protein, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Case-Control Studies, Female, Flow Cytometry, Humans, Inflammation, Killer Cells, Natural, Male, Middle Aged, Receptors, Antigen, T-Cell, T-Lymphocyte Subsets