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Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine.

Wigren, Maria LU ; Kolbus, Daniel LU ; Dunér, Pontus LU ; Ljungcrantz, Irena LU ; Söderberg, Ingrid LU ; Björkbacka, Harry LU orcid ; Nordin Fredrikson, Gunilla LU and Nilsson, Jan LU (2011) In Journal of Internal Medicine 269. p.546-556
Abstract
Abstract. Wigren M, Kolbus D, Dunér P, Ljungcrantz I, Söderberg I, Björkbacka H, Fredrikson GN, Nilsson J. (Malmö University Hospital, Lund University; Malmö University, Malmo; Sweden) Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine. J Intern Med 2010; doi: 10.1111/j.13 65-2796.2010.02311.x. Objectives. Autoimmune responses against oxidized low-density lipoprotein are considered to play an important pro-inflammatory role in atherosclerosis and to promote disease progression. T-regulatory cells (Tregs) are immunosuppressive cells that have an important part in maintaining self-tolerance and protection against autoimmunity. We investigated whether aBp210, a prototype... (More)
Abstract. Wigren M, Kolbus D, Dunér P, Ljungcrantz I, Söderberg I, Björkbacka H, Fredrikson GN, Nilsson J. (Malmö University Hospital, Lund University; Malmö University, Malmo; Sweden) Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine. J Intern Med 2010; doi: 10.1111/j.13 65-2796.2010.02311.x. Objectives. Autoimmune responses against oxidized low-density lipoprotein are considered to play an important pro-inflammatory role in atherosclerosis and to promote disease progression. T-regulatory cells (Tregs) are immunosuppressive cells that have an important part in maintaining self-tolerance and protection against autoimmunity. We investigated whether aBp210, a prototype atherosclerosis vaccine based on a peptide sequence derived from apolipoprotein B, inhibits atherosclerosis through the activation of Tregs. Design. Six-week-old Apoe(-/-) mice were immunized with aBp210 and received booster immunizations 3 and 5 weeks later, as well as 1 week before being killed at 25 weeks of age. Results. At 12 weeks, immunized mice had increased expression of the Treg marker CD25 on circulating CD4 cells, and concanavalin A (Con A)-induced interferon-γ, interleukin (IL)-4, and IL-10 release from splenocytes was markedly depressed. At 25 weeks, there was a fivefold expansion of splenic CD4+ CD25+ Foxp3 Tregs, a 65% decrease in Con A-induced splenic T-cell proliferation and a 37% reduction in the development of atherosclerosis in immunized mice. Administration of blocking antibodies against CD25 neutralized aBp210-induced Treg activation as well as the reduction of atherosclerosis. Conclusions. The present findings demonstrate that immunization of Apoe(-/-) mice with the apolipoprotein B peptide vaccine aBp210 is associated with activation of Tregs. Administration of antibodies against CD25 results in depletion of Tregs and blocking of the atheroprotective effect of the vaccine. Modulation in atherosclerosis-related autoimmunity by antigen-specific activation of Tregs represents a novel approach for treatment of atherosclerosis. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Internal Medicine
volume
269
pages
546 - 556
publisher
Wiley-Blackwell
external identifiers
  • wos:000289641300009
  • pmid:21114693
  • scopus:79954576946
ISSN
1365-2796
DOI
10.1111/j.1365-2796.2010.02311.x
language
English
LU publication?
yes
id
be1375e3-e195-47bc-bef2-a4a829b27094 (old id 1756992)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21114693?dopt=Abstract
date added to LUP
2016-04-04 09:09:07
date last changed
2025-04-04 15:20:20
@article{be1375e3-e195-47bc-bef2-a4a829b27094,
  abstract     = {{Abstract. Wigren M, Kolbus D, Dunér P, Ljungcrantz I, Söderberg I, Björkbacka H, Fredrikson GN, Nilsson J. (Malmö University Hospital, Lund University; Malmö University, Malmo; Sweden) Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine. J Intern Med 2010; doi: 10.1111/j.13 65-2796.2010.02311.x. Objectives. Autoimmune responses against oxidized low-density lipoprotein are considered to play an important pro-inflammatory role in atherosclerosis and to promote disease progression. T-regulatory cells (Tregs) are immunosuppressive cells that have an important part in maintaining self-tolerance and protection against autoimmunity. We investigated whether aBp210, a prototype atherosclerosis vaccine based on a peptide sequence derived from apolipoprotein B, inhibits atherosclerosis through the activation of Tregs. Design. Six-week-old Apoe(-/-) mice were immunized with aBp210 and received booster immunizations 3 and 5 weeks later, as well as 1 week before being killed at 25 weeks of age. Results. At 12 weeks, immunized mice had increased expression of the Treg marker CD25 on circulating CD4 cells, and concanavalin A (Con A)-induced interferon-γ, interleukin (IL)-4, and IL-10 release from splenocytes was markedly depressed. At 25 weeks, there was a fivefold expansion of splenic CD4+ CD25+ Foxp3 Tregs, a 65% decrease in Con A-induced splenic T-cell proliferation and a 37% reduction in the development of atherosclerosis in immunized mice. Administration of blocking antibodies against CD25 neutralized aBp210-induced Treg activation as well as the reduction of atherosclerosis. Conclusions. The present findings demonstrate that immunization of Apoe(-/-) mice with the apolipoprotein B peptide vaccine aBp210 is associated with activation of Tregs. Administration of antibodies against CD25 results in depletion of Tregs and blocking of the atheroprotective effect of the vaccine. Modulation in atherosclerosis-related autoimmunity by antigen-specific activation of Tregs represents a novel approach for treatment of atherosclerosis.}},
  author       = {{Wigren, Maria and Kolbus, Daniel and Dunér, Pontus and Ljungcrantz, Irena and Söderberg, Ingrid and Björkbacka, Harry and Nordin Fredrikson, Gunilla and Nilsson, Jan}},
  issn         = {{1365-2796}},
  language     = {{eng}},
  pages        = {{546--556}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Internal Medicine}},
  title        = {{Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine.}},
  url          = {{http://dx.doi.org/10.1111/j.1365-2796.2010.02311.x}},
  doi          = {{10.1111/j.1365-2796.2010.02311.x}},
  volume       = {{269}},
  year         = {{2011}},
}