BackgroundT cells and macrophages are implicated in the pathogenesis of aortic aneurysm (AA) and atherosclerosis. We recently demonstrated that a vaccine using an apoB-100–related peptide p210 reduces atherosclerosis with favorable modulation of CD8+ T cells in apolipoprotein E–deficient (apoE−/−) mice. ObjectivesThis study hypothesized that a p210 vaccine could reduce AA formation in the angiotensin II (Ang II)–induced AA model. MethodsMale apoE−/− mice were immunized with p210 vaccine and implanted with an Ang II–releasing pump for 4 weeks. Flow cytometry assessed T cell activation and phenotype. Interleukin-6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) expression were assessed using reverse transcription polymerase chain reaction. We used ex vivo aortic explants to test monocyte adhesion and in vitro cocultures to evaluate CD8+ T cell function. ResultsThe p210 vaccine activated CD8+ T cells and reduced AA formation and mortality due to AA rupture, which was attenuated by CD8+ T cell depletion. Vaccination decreased expression of IL-6 and MCP-1 and reduced macrophage infiltration in the aorta. Cytotoxic T-lymphocyte assay showed that CD8+ T cells from p210-immunized mice had higher lytic activity against Ang II–stimulated macrophages. The p210 vaccine decreased splenic Th17 cells, and in vitro coculture of CD4+ and CD8+ T cells showed that CD8+ T cells from p210-immunized mice inhibited the polarization of CD4+ T cells into Th17 cells. IL-17A−/− mice infused with a higher dose of Ang II did not develop AA rupture. ConclusionsA p210 vaccine protected against Ang II–induced AA formation and mortality by reducing macrophage infiltration in the aorta and decreasing Th17 cell polarization. Our findings provide a potentially novel immunomodulating approach against AA.
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