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

Herbin, Olivier; Ait-Oufella, Hafid; Yu, Wang; Nordin Fredrikson, Gunilla LU ; Aubier, Benjamin; Perez, Nicolas; Barateau, Veronique; Nilsson, Jan LU ; Tedgui, Alain and Mallat, Ziad (2012) In Arteriosclerosis, Thrombosis and Vascular Biology 32(3). p.144-605
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... (More)
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.) (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, cytokines, immune system, leukotrienes
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
32
issue
3
pages
144 - 605
publisher
American Heart Association
external identifiers
  • wos:000300639300015
  • scopus:84857653448
ISSN
1524-4636
DOI
10.1161/ATVBAHA.111.242800
language
English
LU publication?
yes
id
24e377b3-148b-4277-90ff-47b4bfd5a2d5 (old id 2390819)
date added to LUP
2012-04-02 09:25:07
date last changed
2017-11-19 03:23:33
@article{24e377b3-148b-4277-90ff-47b4bfd5a2d5,
  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&lt;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.)},
  author       = {Herbin, Olivier and Ait-Oufella, Hafid and Yu, Wang and Nordin Fredrikson, Gunilla and Aubier, Benjamin and Perez, Nicolas and Barateau, Veronique and Nilsson, Jan and Tedgui, Alain and Mallat, Ziad},
  issn         = {1524-4636},
  keyword      = {atherosclerosis,cytokines,immune system,leukotrienes},
  language     = {eng},
  number       = {3},
  pages        = {144--605},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Regulatory T-Cell Response to Apolipoprotein B100-Derived Peptides Reduces the Development and Progression of Atherosclerosis in Mice},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.111.242800},
  volume       = {32},
  year         = {2012},
}