Regulatory T-cell response to apolipoprotein B100-derived peptides reduces the development and progression of atherosclerosis in mice.
Arterioscler Thromb Vasc Biol
; 32(3): 605-12, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22223728
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 ANDRESULTS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Ativação Linfocitária
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Linfócitos T Reguladores
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Aterosclerose
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Apolipoproteína B-100
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Tolerância Imunológica
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Imunoterapia
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article