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

Wigren, Maria LU ; Kolbus, Daniel LU ; Dunér, Pontus LU ; Berg, Katarina LU ; Björkbacka, Harry LU ; Bengtsson, Eva LU ; Nordin Fredrikson, Gunilla LU and Nilsson, Jan LU (2009) In Circulation research 104. p.62-70
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Circulation research
volume
104
pages
62 - 70
publisher
American Heart Association
external identifiers
  • WOS:000267143200014
  • PMID:19478203
  • Scopus:67650215353
ISSN
1524-4571
DOI
10.1161/CIRCRESAHA.109.196667
language
English
LU publication?
yes
id
79d5190c-4402-4ba1-9580-af73edeb0f99 (old id 1411907)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19478203?dopt=Abstract
date added to LUP
2009-06-03 14:54:08
date last changed
2016-10-13 04:27:42
@misc{79d5190c-4402-4ba1-9580-af73edeb0f99,
  abstract     = {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.},
  author       = {Wigren, Maria and Kolbus, Daniel and Dunér, Pontus and Berg, Katarina and Björkbacka, Harry and Bengtsson, Eva and Nordin Fredrikson, Gunilla and Nilsson, Jan},
  issn         = {1524-4571},
  language     = {eng},
  pages        = {62--70},
  publisher    = {ARRAY(0x85ab6f8)},
  series       = {Circulation research},
  title        = {Atheroprotective Effects of Alum Are Associated With Capture of Oxidized LDL Antigens and Activation of Regulatory T Cells.},
  url          = {http://dx.doi.org/10.1161/CIRCRESAHA.109.196667},
  volume       = {104},
  year         = {2009},
}