Document Detail

Induction of neonatal tolerance to oxidized lipoprotein reduces atherosclerosis in ApoE knockout mice.
MedLine Citation:
PMID:  10949909     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In the course of atherosclerosis, humans and apolipoprotein (apoE) Knockout (KO) mice exhibit an active cell-mediated and humoral immune process, both at the systemic level and within atheromata. Low density lipoproteins (LDL) infiltrate the vascular wall, where they are oxidatively modified. This oxidative modification may generate new epitopes for which tolerance is not achieved during ontogenesis. Such epitopes could constitute new targets for autoreactive immune responses that may have a physiopathological role in disease development. MATERIALS AND METHODS: Exposing mice to high dose of antigens during thymic T-cell education induces immunological tolerance to the administered antigens. We injected newborn apoE KO mice with oxidized LDL. They were fed a cholesterol-rich diet and aortic atherosclerosis, cell-mediated immune response, and T-cell repertoire were analyzed after 5 months. RESULTS: Injection of oxidized LDL at birth reduced not only the immune response to oxidized LDL, but also susceptibility to atherosclerosis in apoE mice. Injection of oxidized LDL induced T-cell tolerance due to clonal deletion, rather than anergy of the reactive T cells. The T-cell repertoire of apoE KO mice was affected by the development of the disease, whereas tolerization normalized it. CONCLUSIONS: This study demonstrates that the immune response against oxidized LDL has a deleterious role in atherogenesis and that a fine-tuning of this response could modify the course of the disease.
A Nicoletti; G Paulsson; G Caligiuri; X Zhou; G K Hansson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular medicine (Cambridge, Mass.)     Volume:  6     ISSN:  1076-1551     ISO Abbreviation:  Mol. Med.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-09-06     Completed Date:  2000-09-06     Revised Date:  2008-11-20    
Medline Journal Info:
Nlm Unique ID:  9501023     Medline TA:  Mol Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  283-90     Citation Subset:  IM    
Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
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MeSH Terms
Animals, Newborn / immunology
Antigens, CD / immunology
Aorta / drug effects,  pathology
Apolipoproteins E / deficiency,  genetics,  physiology*
Arteriosclerosis / chemically induced,  genetics,  immunology*,  physiopathology
Cells, Cultured
Cholesterol, Dietary / administration & dosage,  pharmacology
Clonal Deletion / immunology
Diet, Atherogenic
Disease Susceptibility
Epitopes, T-Lymphocyte / immunology
Gene Deletion
Immune Tolerance / immunology*
Immunoglobulins / blood,  immunology
Lipoproteins, LDL / administration & dosage,  immunology*
Mice, Knockout
Receptors, Antigen, T-Cell / genetics,  immunology
T-Lymphocytes / immunology
Reg. No./Substance:
0/Antigens, CD; 0/Apolipoproteins E; 0/Cholesterol, Dietary; 0/Epitopes, T-Lymphocyte; 0/Immunoglobulins; 0/Lipoproteins, LDL; 0/Receptors, Antigen, T-Cell; 0/oxidized low density lipoprotein

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