Correlation between CD4+CD28null T lymphocytes, regulatory T cells and plaque rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes

Aureliano Ruggio, Daniela Pedicino, Davide Flego, Rocco Vergallo, Anna Severino, Claudia Lucci, Giampaolo Niccoli, Carlo Trani, Francesco Burzotta, Cristina Aurigemma, Antonio Maria Leone, Antonino Buffon, Alessia D'Aiello, Luigi Marzio Biasucci, Filippo Crea, Giovanna Liuzzo

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BACKGROUND: A sizeable proportion of patients with Acute Coronary Syndromes (ACS) shows a unique adaptive immune system profile, associated to a worse outcome, characterized by higher CD4+CD28null T-cells, lower regulatory T-cells (Treg) and increased CD4+CD28null/Treg ratio. We sought to investigate the correlation between CD4+CD28null T-cells, Treg, CD4+CD28null/Treg ratio and plaque phenotype as assessed by Optical Coherence Tomography (OCT).

METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 30 Non-ST Elevation Myocardial Infarction (NSTEMI) patients, sub-grouped according to OCT analysis of culprit lesions into two cohorts: Ruptured Fibrous Cap (NSTEMI-RFC, n = 12) and Intact Fibrous Cap (NSTEMI-IFC, n = 18). Stable Angina patients (SA, n = 18) were used as controls. We examined the frequency of CD4+CD28null and Treg (defined as CD4+CD25highCD127lowFoxp3+ T-cells) by flow-cytometry.

RESULTS: CD4+CD28null frequency (median, range) was significantly higher in NSTEMI-RFC patients (17.3%, 12.5-33.8) as compared with NSTEMI-IFC (3.8%, 0.3-14.1) and SA (3%, 0.6-17.7) (P < 0.001 for all comparisons). We also found a higher CD4+CD28null/Treg ratio in NSTEMI-RFC patients (6.6%, 3.7-13.9) than in NSTEMI-IFC (1.6%, 0.3-5.2) and SA (1.2%, 0.3-8.7) (P < 0.001 for all comparisons). Finally, there was an inverse correlation between CD4+CD28null/Treg ratio and cap-thickness (R = -0.44; P = 0.002).

CONCLUSION: Patients with NSTEMI presenting with RFC as culprit lesion at OCT evaluation have a specific perturbation of adaptive immunity, mostly involving CD4+CD28null T- cells and Tregs, as compared with patients with IFC and SA. This specific imbalance of T-cells might play a key role in fibrous cap thinning, predisposing atherosclerotic plaque to rupture.

Original languageEnglish
Pages (from-to)289-292
Number of pages4
JournalInternational Journal of Cardiology
Publication statusE-pub ahead of print - 2018


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