title: Vaccination using oxidized low-density lipoprotein-pulsed dendritic cells reduces atherosclerosis in LDL receptor-deficient mice.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These data indicate that vaccination with oxLDL-pulsed mDCs provides a novel and powerful strategy for the immunomodulation of atherosclerosis.
authors.affiliation: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands. k.habets@lacdr.leidenuniv.nl
authors.forename: Kim L L
authors.initials: KL
authors.lastname: Habets
authors.forename: Gijs H M
authors.initials: GH
authors.lastname: van Puijvelde
authors.forename: Leonie M
authors.initials: LM
authors.lastname: van Duivenvoorde
authors.forename: Eva J A
authors.initials: EJ
authors.lastname: van Wanrooij
authors.forename: Paula
authors.initials: P
authors.lastname: de Vos
authors.forename: Jan-Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: van Berkel
authors.forename: Rene E M
authors.initials: RE
authors.lastname: Toes
authors.forename: Johan
authors.initials: J
authors.lastname: Kuiper
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000628:therapy*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000172:deficiency*; D014611:Vaccination
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol