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Regulatory T-Cell Response to Apolipoprotein B100-Derived Peptides Reduces the Development and Progression of Atherosclerosis in Mice

Author:
  • Olivier Herbin
  • Hafid Ait-Oufella
  • Wang Yu
  • Gunilla Nordin Fredrikson
  • Benjamin Aubier
  • Nicolas Perez
  • Veronique Barateau
  • Jan Nilsson
  • Alain Tedgui
  • Ziad Mallat
Publishing year: 2012
Language: English
Pages: 144-605
Publication/Series: Arteriosclerosis, Thrombosis and Vascular Biology
Volume: 32
Issue: 3
Document type: Journal article
Publisher: Lippincott Williams Wilkins Hagerstown, MD

Abstract english

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. (Arterioscler Thromb Vasc Biol. 2012;32:605-612.)

Keywords

  • Cardiac and Cardiovascular Systems
  • atherosclerosis
  • cytokines
  • immune system
  • leukotrienes

Other

Published
  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 1524-4636
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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