First Author | Chyu KY | Year | 2014 |
Journal | PLoS One | Volume | 9 |
Issue | 3 | Pages | e92095 |
PubMed ID | 24647529 | Mgi Jnum | J:215073 |
Mgi Id | MGI:5604603 | Doi | 10.1371/journal.pone.0092095 |
Citation | Chyu KY, et al. (2014) Cholesterol lowering modulates T cell function in vivo and in vitro. PLoS One 9(3):e92095 |
abstractText | BACKGROUND: The 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 RESULTS: T 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. CONCLUSION: 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. |