Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Jan Nilsson

Professor

Default user image.

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

Summary, in 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.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis

Publishing year

2009

Language

English

Pages

62-70

Publication/Series

Circulation Research

Volume

104

Document type

Journal article

Publisher

American Heart Association

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1524-4571