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

doi:10.1016/j.ijcard.2018.08.101

Correlation between CD4⁺CD28^null T lymphocytes, regulatory T cells and plaque rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes

Int J Cardiol. 2019 Feb 1:276:289-292. doi: 10.1016/j.ijcard.2018.08.101. Epub 2018 Sep 7.

Authors

Aureliano Ruggio¹, Daniela Pedicino¹, Davide Flego¹, Rocco Vergallo¹, Anna Severino¹, Claudia Lucci¹, Giampaolo Niccoli¹, Carlo Trani¹, Francesco Burzotta¹, Cristina Aurigemma¹, Antonio Maria Leone¹, Antonino Buffon¹, Alessia D'Aiello¹, Luigi Marzio Biasucci¹, Filippo Crea¹, Giovanna Liuzzo²

Affiliations

¹ Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
² Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Electronic address: [email protected].

PMID: 30217424
DOI: 10.1016/j.ijcard.2018.08.101

Abstract

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⁺CD28^null T-cells, lower regulatory T-cells (Treg) and increased CD4⁺CD28^null/Treg ratio. We sought to investigate the correlation between CD4⁺CD28^null T-cells, Treg, CD4⁺CD28^null/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⁺CD28^null and Treg (defined as CD4⁺CD25^highCD127^lowFoxp3⁺ T-cells) by flow-cytometry.

Results: CD4⁺CD28^null 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⁺CD28^null/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⁺CD28^null/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⁺CD28^null 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.

Keywords: Acute Coronary Syndromes; Inflammation; Optical Coherence Tomography; Plaque rupture; Precision medicine.

MeSH terms

Acute Coronary Syndrome / diagnosis*
Acute Coronary Syndrome / etiology
Acute Coronary Syndrome / immunology
CD28 Antigens / immunology*
CD4 Antigens / immunology*
Coronary Vessels / pathology*
Follow-Up Studies
Immunity, Cellular
Plaque, Atherosclerotic / complications
Plaque, Atherosclerotic / diagnosis*
Plaque, Atherosclerotic / immunology
Prospective Studies
Rupture, Spontaneous
T-Lymphocytes / immunology
T-Lymphocytes / pathology
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / pathology
Tomography, Optical Coherence / methods*

Substances

CD28 Antigens
CD4 Antigens