CD8+T Cells Elicited by an ApoB-100 Related Peptide Vaccine Mediate Protection Against Angiotension II-induced Hypertension and Renal Fibrosis

Background: T cells play an important role in angiotensin II (AngII)-induced hypertension but the specific subtype involved remains unknown. We recently reported that immunization with apoB-100 related peptide p210 modified CD8+ T cell function, and reduced mean blood pressure (BP) and renal inflammation in AngII-infused apoE (-/-) mice. In this study, we assessed the role of CD8+ T cells in p210 vaccine mediated renal protection. Method 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 subcutaneously implanted with an osmotic pump which released AngII (1 mg/Kg/min), and were euthanized 4 weeks later. Flow cytometric analysis showed p210 treated mice had significantly increased CD8+CD25+IL-12+ splenic T cells indicating CD8+ T cell activation (Table). Renal fibrosis assessed by Masson-Trichrome staining and pro-fibrotic gene expression was significantly reduced in p210 vaccine treated group (Table). P210 immunized mice with CD8+ T cell depletion by a monoclonal antibody (Ab) developed higher mean BP compared to similarly treated mice receiving isotype Ab or no Ab injection ( no Ab injection = 123±1 mmHg, CD8 Ab = 132±1 mmHg*, isotype Ab = 123±2 mmHg, *p<0.05, N=8, 7, 5 respectively, *p<0.05 vs no Ab injection.). Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to no Ab injection (Table). Conclusion: CD8+ T cells elicited by an apoB-100 related peptide vaccine mediate protection against AngII-induced hypertension and renal fibrosis.