Document Detail


T-cell recognition of lipid peroxidation products breaks tolerance to self proteins.
MedLine Citation:
PMID:  10540227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Peroxidation of polyunsaturated fatty acids in lipoproteins and cell membrane phospholipids occurs in many situations in the body, both under normal and pathological conditions. Low-density lipoprotein is particularly prone to oxidation and is believed to be a pathogenetic component in atherogenesis. Both antibody responses and T-cell responses to oxidatively modified lipoproteins have been demonstrated in humans as well as in animal models. However, little is known about how these responses arise or how T cells recognize these antigens. In the present study, mice were immunized with homologous albumin covalently modified with a series of defined aldehydes which are known to be generated during lipid peroxidation. T-cell hybridomas from immunized animals demonstrated major histocompatibility complex-restricted and protein sequence-dependent responses to modified albumin, but not to native albumin. In addition to the response to modified epitopes, some aldehyde modifications resulted in strong antibody responses also to the non-modified protein. This T-cell-dependent break of tolerance constitutes a novel pathway for induction of autoimmunity by lipid peroxidation. The findings have implications in many situations where lipid peroxidation products are generated, including atherosclerosis and inflammatory and infectious diseases.
Authors:
D M Wuttge; M Bruzelius; S Stemme
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  98     ISSN:  0019-2805     ISO Abbreviation:  Immunology     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-11-30     Completed Date:  1999-11-30     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  273-9     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Aldehydes / pharmacology*
Animals
Antigens / administration & dosage
B-Lymphocytes / immunology
Blotting, Western
Female
Hybridomas
Interleukin-2 / immunology
Lipid Peroxidation*
Lymphocyte Activation / drug effects*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Self Tolerance / drug effects*
T-Lymphocytes / immunology*
Chemical
Reg. No./Substance:
0/Aldehydes; 0/Antigens; 0/Interleukin-2
Comments/Corrections

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