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Atheroprotective Effects of Alum Are Associated With Capture of Oxidized LDL Antigens and Activation of Regulatory T Cells.

Author:
  • Maria Wigren
  • Daniel Kolbus
  • Pontus Dunér
  • Katarina Berg
  • Harry Björkbacka
  • Eva Bengtsson
  • Gunilla Nordin Fredrikson
  • Jan Nilsson
Publishing year: 2009
Language: English
Pages: 62-70
Publication/Series: Circulation Research
Volume: 104
Document type: Journal article
Publisher: American Heart Association

Abstract english

The immune system represents a promising novel target for prevention of atherosclerosis. Several pilot vaccines that reduce atherosclerosis in experimental animals have been developed. The aluminum hydroxide adjuvant Alum has been shown to have antiatherogenic properties in itself, suggesting that it may be a suitable adjuvant in possible future atherosclerosis vaccines. To characterize the immune pathways mediating this protection, we treated wild-type C57BL/6 and Apoe(-/-) mice with Alum or PBS. Analyses of splenocytes isolated from 12-week-old mice demonstrated that Alum increased the presence of CD4(+)CD25(+)FoxP3(+) regulatory T cells and downregulated the expression of T cell activation markers CD28 and ICOS in Apoe(-/-) mice but not in C57BL/6 wild-type mice. A similar immunosuppressive phenotype was found also in 25-week-old Apoe(-/-) mice and was associated with reduced atherosclerosis. Alum precipitates recovered from the injection site of Apoe(-/-) mice contained antigens derived from oxidized LDL. These findings demonstrate that treatment of Apoe(-/-) mice with Alum results in an increase of regulatory T cells and suggest that these are activated by tolerogenic antigen-presenting cells presenting oxidized LDL antigens. Our findings provide improved mechanistic understanding of the atheroprotective properties of aluminum hydroxide adjuvants but also point to the importance of determining if hypercholesterolemia may compromise the efficacy of Alum-containing vaccines used clinically today.

Keywords

  • Cardiac and Cardiovascular Systems

Other

Published
  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 1524-4571
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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