title: Immunotherapy with tolerogenic apolipoprotein B-100-loaded dendritic cells attenuates atherosclerosis in hypercholesterolemic mice.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory disease characterized by a massive intimal accumulation of low-density lipoprotein that triggers chronic vascular inflammation with an autoimmune response to low-density lipoprotein components.
  
  
  RESULTS
  To dampen the inflammatory component of atherosclerosis, we injected hypercholesterolemic huB100(tg) × Ldlr(-/-) mice (mice transgenic for human apolipoprotein B100 [ApoB100] and deficient for the low-density lipoprotein receptor) intravenously with dendritic cells (DCs) that had been pulsed with the low-density lipoprotein protein ApoB100 in combination with the immunosuppressive cytokine interleukin-10. DCs treated with ApoB100 and interleukin-10 reduced proliferation of effector T cells, inhibited production of interferon-γ, and increased de novo generation of regulatory T cells in vitro. Spleen cells from mice treated with DCs plus ApoB100 plus interleukin-10 showed diminished proliferative responses to ApoB100 and significantly dampened T-helper 1 and 2 immunity to ApoB100. Spleen CD4(+) T cells from these mice suppressed activation of ApoB100-reactive T cells in a manner characteristic of regulatory T cells, and mRNA analysis of lymphoid organs showed induction of transcripts characteristic of these cells. Treatment of huB100(tg) × Ldlr(-/-) mice with ApoB100-pulsed tolerogenic DCs led to a significant (70%) reduction of atherosclerotic lesions in the aorta, with decreased CD4(+) T-cell infiltration and signs of reduced systemic inflammation.
  
  
  CONCLUSIONS
  Tolerogenic DCs pulsed with ApoB100 reduced the autoimmune response against low-density lipoprotein and may represent a novel possibility for treatment or prevention of atherosclerosis.
authors.affiliation: Department of Medicine at Karolinska University Hospital Solna, Karolinska Institutet, Center for Molecular Medicine, Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hermansson
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Johansson
authors.forename: Daniel F J
authors.initials: DF
authors.lastname: Ketelhuth
authors.forename: John
authors.initials: J
authors.lastname: Andersson
authors.forename: Xinghua
authors.initials: X
authors.lastname: Zhou
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology; D053299:Apolipoprotein B-100 / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000276:immunology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D006937:Hypercholesterolemia / Q000276:immunology / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D053299:Apolipoprotein B-100; D016753:Interleukin-10; D007371:Interferon-gamma