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

Abstract

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