Abstract
BackgroundThe lipid milleu exacerbates the inflammatory response in atherosclerosis but its effect on T cell mediated immune response has not been fully elucidated. We hypothesized that lipid lowering would modulate T cell mediated immune function.Methods and ResultsT cells isolated from human PBMC or splenic T cells from apoE-/- mouse had higher proliferative response to T cell receptor (TCR) ligation in medium supplemented with 10% fetal bovine serum (FBS) compared to medium with 10% delipidated FBS. The differences in proliferation were associated with changes in lipid rafts, cellular cholesterol content, IL-10 secretion and subsequent activation of signaling molecule activated by TCR ligation. Immune biomarkers were also assessed in vivo using male apoE-/- mice fed atherogenic diet (AD) starting at 7 weeks of age. At 25 weeks of age, a sub-group was switched to normal diet (ND) whereas the rest remained on AD until euthanasia at 29 weeks of age. Dietary change resulted in a lower circulating level of cholesterol, reduced plaque size and inflammatory phenotype of plaques. These changes were associated with reduced intracellular IL-10 and IL-12 expression in CD4+ and CD8+ T cells.ConclusionOur results show that lipid lowering reduces T cell proliferation and function, supporting the notion that lipid lowering modulates T cell function in vivo and in vitro.
Highlights
Pharmacological lipid lowering using statins is the primary medical therapy to reduce morbidity and mortality from atherosclerotic cardiovascular disease
Our results show that lipid lowering reduces T cell proliferation and function, supporting the notion that lipid lowering modulates T cell function in vivo and in vitro
At the age of 25 weeks, one group of mice was switched to normal chow diet (ND mice) and another group remained on atherogenic diet (AD mice)
Summary
Pharmacological lipid lowering using statins is the primary medical therapy to reduce morbidity and mortality from atherosclerotic cardiovascular disease. This beneficial effect has been attributed to the plaque-stabilizing effects of cholesterol lowering accompanied by reduced inflammatory phenotype of atherosclerotic plaques as demonstrated both in clinical [1,2,3] and preclinical studies [4,5]. Dietary modification to lower circulating cholesterol level is another effective strategy to modify atherosclerotic cardiovascular diseases. This benefit has been primarily attributed to its cholesterol lowering effect; whether such cholesterol lowering affects T cell function remains unknown. We hypothesized that lipid lowering would modulate T cell mediated immune function
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