Abstract
ObjectiveCD4+ latency-associated peptide (LAP)+ regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4+LAP+ Tregs are defective in ACS.MethodsOne hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4+LAP+ Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4+ T cells were determined by flow cytometry. The function of CD4+LAP+ Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction.ResultsWe found ACS patients had a significantly lower frequency of circulating CD4+LAP+ Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4+ T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts.ConclusionsA novel regulatory T cell subset, defined as CD4+LAP+ T cells is defective in ACS patients.
Highlights
Atherosclerosis is a chronic inflammatory disease involving immunologic imbalance
Previous studies have shown that naturally occurring CD4+CD25+ Tregs are down-regulated in patients with acute coronary syndrome (ACS) [9,10,11]
There were no significant differences in age, gender, diabetes mellitus status, hypercholesterolemic status, or the use of aspirin or calcium blockers, or smoking status among the patients with ACS, chronic stable angina (CSA), or chest pain syndrome (CPS) groups
Summary
Macrophagocyte, monocyte, lymphocyte especially T lymphocytes participate in the chronic inflammatory reaction and lead to the occurrence and development of acute coronary syndrome (ACS) [1,2,3,4]. In order for latent TGF-b to become active, the mature TGF- b must be released from LAP [16,17,18]. The CD4+LAP+ T cells lack Foxp expression, but they function to the classical CD4+CD25+FOXP3+ Tregs and produce a suppressive effect on immune response. CD4+LAP+ T cells have been shown to suppress murine autoimmunity in experimental models of encephalomyelitis, systemic lupus erythematosus, colitis, and diabetes [24,25,26,27,28,29,30]. GARP binds directly to LAP and tethers latent TGF-b on the surface of activated Tregs, and it has been clarified that GARP is a receptor for latent TGF-b [22,23]
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