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Publication : Cholesterol lowering modulates T cell function in vivo and in vitro.

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.
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