Abstract
BackgroundThe CD4+ T-lymphocytes and their subtype CD4 + CD25highFoxP3+ regulatory T cells are receiving growing interest as major regulators of atherogenesis. We sought to investigate 1) whether the CD4 + cell subsets were expressed differently in dyslipidemic patients (Pts) and healthy subjects (HS) and 2) whether atorvastatin treatment could be associated in-vivo and in-vitro with cell changes in expression and functional response.MethodsCD4+ subsets frequency (CD4 + CD25highFoxP3+, CD4 + CD25-FoxP3+) and mRNA expression for FoxP3, IL-10 and TGF-β were evaluated in 30 consecutive Pts at baseline and after a 3-month atorvastatin therapy, and in 17 HS.ResultsThe % of CD4 + cells did not differ between HS and Pts. The % of CD4 + CD25highFoxP3+ was higher in Pts than HS and did not change during treatment. The CD4 + CD25-FoxP3+ cells were similar between the two groups and were lower in Pts at visit 2. Cytokine expression and FoxP3 did not differ in HS and Pts and no substantial change was observed during treatment. At visit 1, CD4 + CD25highFoxP3+ cells were significantly correlated with both total-cholesterol (r = 0.570, P = 0.0002), LDL-cholesterol (r = 0.715, P = 0.0001), Apolipoprotein B (r = 0.590, P = 0.0001). In-vitro atorvastatin (up to 5 μM) failed to induce any significant modulation of cell functions.ConclusionCD4 + CD25highFoxP3+ regulatory cells seem to be over-stimulated in the early pre-clinical phase of atherosclerosis and a relationship exists between their frequency and circulating lipids. A potential immuno-modulation by statin treatment is not achieved through a normalization in peripheral CD4 + cell subsets.
Highlights
The CD4+ T-lymphocytes and their subtype CD4 + CD25highFoxP3+ regulatory T cells are receiving growing interest as major regulators of atherogenesis
Effect of 3-month treatment with atorvastatin on cell subsets of dyslipidemic Pts and comparison with healthy subjects (HS) Clinical and laboratory parameters in Pts and HS Mean age and gender distribution were similar in Pts and HS (49 ± 9 vs 45 ± 8 years, P = 0.21; 80 % males vs 65 %), as well as body mass index (BMI) and waist circumference (WC) [(BMI 26.8 ± 4 vs 23.7 ± 3.4 kg/m2 (P = 0.07); WC 97.4 ± 10.6 vs 87.3 ± 10.7 cm (P = 0.052)]
Values measured in Pts at visit 1 were significantly different with respect to values measured in HS fot TotC, LDLc, Apolipoprotein B (ApoB) and TG
Summary
The CD4+ T-lymphocytes and their subtype CD4 + CD25highFoxP3+ regulatory T cells are receiving growing interest as major regulators of atherogenesis. We sought to investigate 1) whether the CD4 + cell subsets were expressed differently in dyslipidemic patients (Pts) and healthy subjects (HS) and 2) whether atorvastatin treatment could be associated in-vivo and in-vitro with cell changes in expression and functional response. A potential immuno-modulation by statin treatment is not achieved through a normalization in peripheral CD4 + cell subsets. We sought to investigate in dyslipidemic subjects bearing an increased risk for vascular events whether the CD4+ cell subsets, including specific T cell subsets known to be involved in the immune-response regulation, such as T cells characterized as CD4 + CD25highFoxP3+, were differently expressed compared to controls. We evaluated whether atorvastatin ex vivo and in vitro treatment could be associated with changes in expression and functional response of CD4+ T cell subsets
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