Clonal restriction and predominance of regulatory T cells in coronary thrombi of patients with acute coronary syndromes
| Autor: | Anais Courtier, Anika Lewandowski, Nicolas Pasqual, Roland Klingenberg, Milosz Jaguszewski, Eugenia Vlaskou Badra, Oliver Gaemperli, Willibald Maier, Chad Brokopp, Thomas F. Lüscher, Audrey Grives, Simon P. Hoerstrup, Christian M. Matter, Ulf Landmesser |
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| Přispěvatelé: | University of Zurich, Klingenberg, Roland |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Lymphocytosis T cell Receptors Antigen T-Cell alpha-beta Myocardial Infarction T cells 610 Medicine & health chemical and pharmacologic phenomena Acute coronary syndromes T-Lymphocytes Regulatory 2705 Cardiology and Cardiovascular Medicine Immune system Antigen Basic Science Medicine Humans IL-2 receptor Lymphocyte Count Acute Coronary Syndrome Gene Rearrangement beta-Chain T-Cell Antigen Receptor Aged business.industry Coronary Thrombosis T-cell receptor Immunity hemic and immune systems T lymphocyte Middle Aged Acquired immune system Flow Cytometry 3. Good health medicine.anatomical_structure 10076 Center for Integrative Human Physiology Immunology 10209 Clinic for Cardiology Leukocytes Mononuclear 570 Life sciences biology medicine.symptom Cardiology and Cardiovascular Medicine business |
| Zdroj: | EUROPEAN HEART JOURNAL European Heart Journal |
| DOI: | 10.1093/eurheartj/eht543 |
| Popis: | Aims Regulatory T cells (Treg) exert anti-inflammatory and atheroprotective effects in experimental atherosclerosis. Treg can be induced against specific antigens using immunization strategies associated with clonal restriction. No data exist on Treg in combination with clonal restriction of T cells in patients with acute coronary syndromes (ACS). Methods and results Among T cell subsets characterized by flow cytometry, Treg (CD4+ CD25+ CD127low) were twice as frequent in coronary thrombi compared with peripheral blood. Treg prevailed among T cell subsets identified in coronary thrombi. To evaluate clonal restriction, genomic DNA was extracted from coronary thrombi and peripheral blood in order to evaluate T cell receptor (TCR) β chain diversity by means of Multi-N-plex PCR using a primer specific for all TCR β V gene segments and another primer specific for TCR β J gene segments. T cell receptor diversity was reduced in thrombi compared with peripheral blood (intra-individual comparisons in 16 patients) with 8 gene rearrangements in the TCR common in at least 6 out of 16 analysed coronary thrombi. Compared with age-matched healthy controls ( n = 16), TCR diversity was also reduced in peripheral blood of patients with ACS; these findings were independent of peripheral T cell numbers. Conclusion We provide novel evidence for a perturbed T cell compartment characterized by clonal restriction in peripheral blood and coronary thrombi from patients with ACS. Our findings warrant further studies on Treg as novel therapeutic targets aimed at enhancing this anti-inflammatory component of adaptive immunity in human atherothrombosis. |
| Databáze: | OpenAIRE |
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