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  • Title: Atheroprotective immunization with MDA-modified apo B-100 peptide sequences is associated with activation of Th2 specific antibody expression.
    Author: Fredrikson GN, Andersson L, Söderberg I, Dimayuga P, Chyu KY, Shah PK, Nilsson J.
    Journal: Autoimmunity; 2005 Mar; 38(2):171-9. PubMed ID: 16040338.
    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-gamma expression.
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