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Vaccination against...
Vaccination against T-cell epitopes of native ApoB100 reduces vascular inflammation and disease in a humanized mouse model of atherosclerosis
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- Gisterå, A. (författare)
- Karolinska Institutet,Karolinska Institute
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- Hermansson, A. (författare)
- Karolinska Institute
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- Strodthoff, Daniela (författare)
- Karolinska Institute
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- Klement, M. L. (författare)
- Karolinska Institute
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- Hedin, Ulf (författare)
- Karolinska Institutet
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- Fredrikson, G. N. (författare)
- Skåne University Hospital
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- Nilsson, J. (författare)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Hansson, G. K. (författare)
- Karolinska Institutet,Karolinska Institute
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- Ketelhuth, Daniel F. J. (författare)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- 2017-02-13
- 2017
- Engelska.
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 281:4, s. 383-397
- Relaterad länk:
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http://dx.doi.org/10...
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https://onlinelibrar...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background and Objectives: The T-cell response to low-density lipoprotein (LDL) in the vessel wall plays a critical role in atherosclerotic plaque formation and stability. In this study, we used a new translational approach to investigate epitopes from human apolipoprotein B100 (ApoB100), the protein component of LDL, which triggers T-cell activation. We also evaluated the potential of two selected native ApoB100 epitopes to modulate atherosclerosis in human ApoB100-transgenic Ldlr-/- (HuBL) mice. Methods and Results: HuBL mice were immunized with human atherosclerotic plaque homogenate to boost cellular autoimmune response to tissue-derived ApoB100 epitopes. In vitro challenge of splenocytes from immunized mice with a library of overlapping native peptides covering human ApoB100 revealed several sequences eliciting T-cell proliferation. Of these sequences, peptide (P) 265 and P295 were predicted to bind several human leucocyte antigen (HLA) haplotypes and induced high levels of interferon (IFN)-γ. Vaccination of HuBL mice with these peptides mounted a strong adaptive immune response to native ApoB100, including high levels of epitope-specific plasma IgGs. Interestingly, P265 and P295 vaccines significantly decreased plaque size, reduced macrophage infiltration and increased IgG1 deposition in the plaques. Purified IgGs from vaccinated mice displayed anti-inflammatory properties against macrophages in vitro, reducing their response to LPS in a dose-dependent manner. Conclusion: We identified two specific epitopes from human native ApoB100 that trigger T-cell activation and protect HuBL mice against atherosclerosis when used in a vaccine. Our data suggest that vaccination-induced protective mechanisms may be mediated at least in part through specific antibody responses to LDL that inhibit macrophage activation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- Apolipoprotein B-100
- Atherosclerosis
- Epitopes
- T-cell
- Vaccination
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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