Abstract 11654: Lipid Lowering Modulates T cell Function in vivo and in vitro
Background: The lipid milleu exacerbates the inflammatory response in atherosclerosis but the effects on the adaptive immune response has not been fully elucidated. We hypothesized that lipid lowering would confer favorable effects on the adaptive immune function, measurable by immune biomarkers that correlate with disease severity.
Methods and Results: Immune biomarkers were assessed in vivo using male apoE-/- mice fed atherogenic diet (AD) starting at 6 weeks of age. At 25 weeks of age, a sub-group was switched to normal diet (ND) whereas the rest remained on AD. Mice were euthanized at 29 weeks of age and the spleen was collected for T cell analysis. There were significantly less T cells positive for intracellular IL-10 and IL-12 expression with diet change (Table; N=10 each group; all p<0.05 by t-test). CD4 and CD8 T cells positive for IL-10 or IL-12 correlated with total cholesterol levels (P<0.05, Spearman). Neither en face atherosclerosis nor aortic sinus plaque size correlated with intracellular cytokines. Splenic T cells from apoE-/- mouse had a higher rate of proliferation when cultured in medium with 10% normal FBS compared to 10% delipidated FBS (CD4: 48.9±8.3% vs 33.2±9.1%, respectively, n=5 each, p<0.05; CD8: 56.9±6.2% vs 29.2±14.5%, respectively, n=4 each; p<0.05). T cells isolated from human PBMC also had higher proliferative response in medium with 10% normal FBS compared to 10% delipidated FBS (CD4: 74.5±2.5% vs 42.9±7.0%, respectively, n=5 each, p<0.05; CD8: 88.8±5.2% vs 63.2±17.0%, n=5 each; p<0.05). The differences in proliferation were not associated with changes in lipid rafts, assessed by fluorescently labeled CTB, suggesting alternative signaling pathways.
Conclusion: Our results show that reduced cholesterol levels correlate with reduced intracellular IL-10 and IL-12 expression in T cells. Though a reduced lipid milleu reduced T cell proliferation and function, the effect appears to be independent of changes in lipid raft density. Table
- © 2011 by American Heart Association, Inc.