Regulatory T-Cell Response to Apolipoprotein B100–Derived Peptides Reduces the Development and Progression of Atherosclerosis in Mice
Objective—The immunoinflammatory response plays a critical role in the development and progression of atherosclerosis. Recent studies suggested an important role for regulatory T (Treg) cells in the inhibition of disease-related vascular inflammation. We hypothesized that induction of a specific Treg cell response to atherosclerosis-relevant antigens would be an attractive strategy to limit the development and progression of atherosclerosis through the promotion of immune tolerance.
Methods and Results—Young or old Apoe−/− mice were subcutaneously infused for 2 weeks with either a control ovalbumin (OVA) peptide or with apolipoprotein B100 (ApoB100)–derived peptides without adjuvant. Atherosclerosis development, progression and immunologic status were assessed at 8 weeks after the end of the infusion. Treatment with ApoB100 peptides led to significant reduction of lesion development in young Apoe−/− mice (P=0.001 versus OVA group) and abrogated atherosclerosis progression in old Apoe−/− mice with already established lesions (0% progression in ApoB100 versus 17% in OVA group, P<0.005). Limitation of plaque progression was associated with reduced vascular inflammation and increased collagen content, indicative of plaque stabilization. Infusion of ApoB100 peptides did not alter antibody production but promoted a specific Treg cell response, which was associated with a reduction of both T helper type 1–related and T helper type 2–related cytokines. Interestingly, depletion of CD4+CD25+ Treg cells abrogated ApoB100 peptides-dependent immune modulation and atheroprotection.
Conclusion—Subcutaneous infusion of adjuvant-free ApoB100-derived peptides to Apoe−/− mice reduces atherosclerosis through the induction of a specific Treg cell response.
- Received October 4, 2011.
- Accepted December 16, 2011.
- © 2012 American Heart Association, Inc.