Abstract 13428: Cell Depletion Studies Identify CD8+ T cells as Mediators of Beneficial Effects of p210 Vaccination in Angiotensin-II Induced Aortic Aneurysm Formation and Rupture
Background: We previously reported that vaccination with an apoB-100 peptide called p210 markedly reduced angiotensin-II (AngII) induced aortic aneurysm (AA) formation and mortality from AA rupture in apoE-/- mice. The cellular mediators involved have, however, not been clearly defined. We have also shown that the athero-protective effects of p210 immunization are mediated by modulation of CD8+ T cells. To determine the mechanistic role of CD8+ T cells in the protective effect of p210 immunization in AngII induced AA, we performed experiments depleting CD8+ T cells in p210 immunized mice.
Methods and Results: ApoE-/- mice were immunized with the p210 vaccine at 7, 10, and 12 weeks of age. At 10 weeks of age, AngII was infused using an osmotic pump at a dose of 1000ng/kg/min for 4 weeks. Mice were injected with either a CD8 depleting antibody (CD8 Ab) or control IgG (Isotype) at a dose of 150μg 3 days before the first immunization and then twice a week thereafter. Splenocytes collected at euthanasia confirmed nearly 50% depletion of CD8+ T cells in the CD8 Ab group compared to Isotype (4.0±0.7% N=5 vs. 7.7±1.6% N=11, respectively; P<0.01). There was significant mortality from AA rupture in the CD8 Ab group (N=14) compared to Isotype group (N=13) at 14 and 21 days (P<0.05; Figure 1). CD8 Ab mortality was similar to AngII-infused naïve mice with no antibody injections (73% survival at 14 and 21 days, 64.9% at 28 days). Mean aortic diameter was significantly higher in the CD8 Ab group compared to Isotype (1.04±0.12 mm2 vs. 0.84±0.14mm2, respectively; P<0.05). Splenic Th17 cells were significantly increased in CD8 Ab group compared to Isotype (1.14±0.61% N=3 vs. 0.55±0.20% N=11, respectively; P<0.05).
Conclusion: Depletion of CD8+ T cells attenuated the protective effects of the p210 vaccine against aneurysm rupture and death, with increase in Th17 cells. The study confirms the role of CD8+ T cells in the protective effect of p210 immunization against aortic aneurysm formation and rupture.
Author Disclosures: T. Honjo: None. P.C. Dimayuga: None. K. Chyu: None. J. Yano: None. W. Lio: None. X. Zhao: None. J. Zhou: None. B. Cercek: None. P.K. Shah: Consultant/Advisory Board; Modest; scientific advisor, Cardiovax.
- © 2014 by American Heart Association, Inc.