Regulatory T-Cell Response to Apolipoprotein B100-Derived Peptides Reduces the Development and Progression of Atherosclerosis in Mice
(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:
https://lup.lub.lu.se/record/2390819
- author
- 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
- organization
- publishing date
- 2012
- 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
- Lippincott Williams & Wilkins
- 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
- 2016-04-01 11:13:30
- date last changed
- 2022-04-28 08:12:13
@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<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}}, keywords = {{atherosclerosis; cytokines; immune system; leukotrienes}}, language = {{eng}}, number = {{3}}, pages = {{144--605}}, publisher = {{Lippincott Williams & Wilkins}}, 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}}, doi = {{10.1161/ATVBAHA.111.242800}}, volume = {{32}}, year = {{2012}}, }