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Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease
Author(s) -
Hasib L.,
Lundberg A. K.,
Zachrisson H.,
Ernerudh J.,
Jonasson L.
Publication year - 2016
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12398
Subject(s) - medicine , homeostasis , coronary artery disease , secretion , cytokine , flow cytometry , immunology , inflammation , lipopolysaccharide , acute coronary syndrome , myocardial infarction
Objective Regulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome ( ACS ), particularly non‐ ST elevation ( NSTE )‐ ACS . However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease ( CAD ). Here, we investigated the composition and functional properties of naïve (n) and memory (m)Tregs in patients with NSTE ‐ ACS and in patients 6–12 months post‐ ACS . Methods Based on the expression of CD 25, FOXP 3, CD 127, CD 45 RA , CD 39 and CTLA ‐4, Treg subsets were defined by flow cytometry in whole blood or isolated CD 4 + T cells. The functional properties of nT regs and mT regs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide ( LPS )‐induced cytokine secretion and ultrasound‐defined carotid atherosclerosis. Results Both NSTE ‐ ACS and post‐ ACS patients exhibited reduced levels of nT regs ( P < 0.001) compared with healthy control subjects, but without compensatory increases in mT regs. Both nT regs and mT regs from patients showed significantly lower replicative rates and impaired capacity to modulate T‐cell proliferation and secretion of interferon‐gamma and IL ‐10. The Treg defect was also associated with LPS ‐induced cytokine secretion and increased burden of carotid atherosclerosis. Conclusion Our results demonstrate a functional and homeostatic Treg defect in patients with NSTE ‐ ACS and also in stabilized patients 6–12 months after ACS . Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune‐restoring strategies in CAD .