Abstract 13017: CD8+ T Cells Elicited by an ApoB-100 Related Peptide Vaccine Protect Against Angiotension II-induced Aortic Aneurysm Formation by Inhibiting Aortic Macrophage Infiltration and Modulating Th17 Polarization
Background: We have reported that atheroprotective effects of an apoB-100 related peptide p210 vaccine are mediated by CD8+ T cells. We recently demonstrated that p210 vaccine reduces aortic aneurysm (AA) formation in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we assessed the role of CD8+ T cells in p210 vaccine mediated AA protection.
Methods and Results: ApoE (-/-) mice were immunized with p210/cBSA/Alum (p210; 100 μg) at 7, 10, and 12 weeks of age. Mice receiving PBS or cBSA/Alum (cBSA) served as controls. At 10 weeks of age, mice were implanted with an AngII-releasing osmotic pump (1mg/Kg/min), and euthanized 4 weeks later. P210 vaccinated mice had significantly increased splenic CD8+CD25+IL12+ T cells and decreased CD4+IL17A+ (Th17) cells (Table). Aortic adventitial macrophage infiltration was significantly decreased in p210 group (MOMA-2 stain, Table). CD8+ T cell cytotoxic assays with AngII-stimulated peritoneal macrophages as targets showed that CD8+ T cells from p210 group had significantly higher lytic activity (Table). Ex vivo adhesion assay showed that significantly less monocytes from p210 group adhered to AngII-treated aorta from naïve apoE(-/-) mice (Table). P210 vaccine also reduced aortic IL-6 and MCP-1 mRNA expression (Table). In vitro co-culture of CD4+ and CD8+ T cells showed that CD8+ T cells from p210 group significantly inhibited the polarization of CD4+ T cells into Th17 cells (PBS = 0.40±0.03*, cBSA = 0.32±0.01*, p210 = 0.23±0.03, without CD8 = 0.19 ± 0.04 %, N=3 each, *p≤0.05 vs p210). IL17A (-/-) mice infused with higher dose of AngII (2.5mg/Kg/min) did not develop AA.
Conclusion: P210 vaccine attenuated the infiltration of monocyte/macrophage in aortic wall through increased CD8+ T cell mediated lytic activity and inhibition of CD4+ T cell polarization to Th17 cells, associated with down-regulation of aortic IL-6 and MCP-1 expression. CD8+ T cells appear to have an important role in anti-aneurysmal effect of p210 vaccine.
- © 2013 by American Heart Association, Inc.