Vaccination using oxidized low-density lipoprotein-pulsed dendritic cells reduces atherosclerosis in LDL receptor-deficient mice

Kim L. Habets*, Gijs H. M. van Puijvelde, Leonie M. van Duivenvoorde, Eva J. A. van Wanrooij, Paula de Vos, Jan Willem Cohen Tervaert, Theo J. C. van Berkel, Rene E. M. Toes, Johan Kuiper

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Aims Modification of lipoproteins plays an important role in the development of atherosclerosis. Oxidatively modified low-density lipoprotein (oxLDL) has a number of pro-inflammatory effects, whereas immunization with various forms of oxLDL is able to reduce atherosclerosis. The uptake of modified LDL by dendritic cells (DCs) and the presentation of epitopes thereof may form an important step in the immunomodulatory effects of LDL. In this study, we transferred oxLDL-pulsed mature DCs (mDCs) to LDL receptor-null (LDLr(-/-)) mice and examined the effects on atherosclerosis. Methods and results Bone marrow-derived DCs were cultured for 10 days in the presence of granulocyte-macrophage colony-stimulating factor. Immature DCs were matured by lipopolysaccharide and pulsed with copper-oxidized LDL. These mDCs were transferred three times to LDLr(-/-) mice before the induction of atherosclerosis by Western-type diet feeding. The transfer of oxLDL-pulsed mDCs resulted in an 87% reduction in carotid artery lesion size (P <0.001) with a concurrent increase in plaque stability, whereas treatment using mDCs pulsed with the atherosclerosis-irrelevant antigen, ovalbumin, did not influence lesion size or stability. Furthermore, the vaccination procedure resulted in the induction of oxLDL-specific T cells with a reduced Th1 profile and an increase in oxLDL-specific IgG levels, which contributed to a reduction in foam cell formation. Conclusion These data indicate that vaccination with oxLDL-pulsed mDCs provides a novel and powerful strategy for the immunomodulation of atherosclerosis.
Original languageEnglish
Pages (from-to)622-630
JournalCardiovascular Research
Volume85
Issue number3
DOIs
Publication statusPublished - 1 Feb 2010

Keywords

  • Atherosclerosis
  • Immunotherapy
  • Dendritic cells
  • Antigen-presenting cells

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