Atheroprotective immunization with MDA-modified apo B-100 peptide sequences is associated with activation of Th2 specific antibody expression
- 1 March 2005
- journal article
- research article
- Published by Taylor & Francis Ltd in Autoimmunity
- Vol. 38 (2), 171-179
- https://doi.org/10.1080/08916930500050525
Abstract
Objective: The objective of this study was to evaluate if immunization with MDA-modified human apo B-100 fragments is associated with a shift in the Th1/Th2 balance. Methods and Results: Apo E deficient mice were immunized with one of the peptides (P45; amino acids 688–707, P74; amino acids 1123–1142 or P240; amino acids 3613–3632) at 6, 9 and 11 weeks of age and compared to controls given carrier alone. Immunization with P45 and P74 reduced atherosclerosis in the aorta of 25-week-old mice by 48% (p=0.02) and 31% (p=0.06) and macrophage content in atherosclerotic plaques by 33% (p=0.02) and 39% (p=0.02), respectively. The levels of Th2-specific IgG1 against each peptide increased more than 50-fold in response to immunization, whereas the levels of specific IgM and Th1-associated IgG2a were only marginally affected. However, there was an increase in the plaque expression of both Th1 and Th2 cytokines as assessed by real time PCR. Immunization with P240, a non-homologous peptide used as control, induced a 10-fold increase of specific IgG1 but did not influence atherosclerosis or plaque content. Conclusions: Immunization with MDA apo B-100 fragments induce a shift from Th1 to a Th2 specific oxidized LDL antibody expression, but without a concomitant downregulation of plaque IFN-γ expression.Keywords
This publication has 13 references indexed in Scilit:
- Identification of Immune Responses Against Aldehyde-Modified Peptide Sequences in ApoB Associated With Cardiovascular DiseaseArteriosclerosis, Thrombosis, and Vascular Biology, 2003
- Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloidInternational Immunology, 2003
- Innate and acquired immunity in atherogenesisNature Medicine, 2002
- Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunityJCI Insight, 2000
- Monoclonal antibodies against oxidized low-density lipoprotein bind to apoptotic cells and inhibit their phagocytosis by elicited macrophages: Evidence that oxidation-specific epitopes mediate macrophage recognitionProceedings of the National Academy of Sciences of the United States of America, 1999
- Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice.JCI Insight, 1998
- Effect of Immunization With Homologous LDL and Oxidized LDL on Early Atherosclerosis in Hypercholesterolemic RabbitsArteriosclerosis, Thrombosis, and Vascular Biology, 1996
- Autoantibody against oxidised LDL and progression of carotid atherosclerosisThe Lancet, 1992
- Induction of T-cell activation by oxidized low density lipoprotein.Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1992
- Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein.Arteriosclerosis: An Official Journal of the American Heart Association, Inc., 1990