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. 2012 Mar;32(3):605-12.
doi: 10.1161/ATVBAHA.111.242800. Epub 2012 Jan 5.

Regulatory T-cell response to apolipoprotein B100-derived peptides reduces the development and progression of atherosclerosis in mice

Olivier Herbin  1 , Hafid Ait-Oufella, Wang Yu, Gunilla Nordin Fredrikson, Benjamin Aubier, Nicolas Perez, Véronique Barateau, Jan Nilsson, Alain Tedgui, Ziad Mallat
Affiliations

Regulatory T-cell response to apolipoprotein B100-derived peptides reduces the development and progression of atherosclerosis in mice

Olivier Herbin et al. Arterioscler Thromb Vasc Biol. 2012 Mar.

Abstract

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 alterantibody 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.

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