title: Subcutaneous immunization with heat shock protein-65 reduces atherosclerosis in Apoe⁻/⁻ mice.
abstract: OBJECTIVE
  To modulate atherosclerosis by combining subcutaneous immunization with heat shock protein 65 (hsp65) in alum adjuvant and anti-CD45RB monoclonal antibodies (mAb).
  
  
  METHODS
  8 week old Apoe⁻/⁻ mice on normal chow were treated for 12 weeks: group A received hsp65-alum immunization combined with anti-CD45RB mAb, group B hsp65-alum immunization combined with isotype control antibody, and group C mock vaccine combined with isotype control antibody.
  
  
  RESULTS
  Unexpectedly, atherosclerotic lesions in the aortic root were significantly reduced in both hsp65-alum immunization groups (A and B) compared with the control group (C). Significantly elevated antibody titers against hsp65 were detected in both groups along with a significant increase in MHC class II expression on B cells. Body weight, total cholesterol and triglyceride levels were not different between groups. Treatment with anti-CD45RB antibody mediated a shift on CD4⁺ T cells from the CD45RB(high) to CD45RB(low) isoform with a relative increase in CD4⁺Foxp3⁺ regulatory T cells (Treg) in an overall reduced T cell pool. Furthermore, anti-CD45RB treatment mediated a transient reduction of peripheral leukocytes and increased IFN-γ and IL-17A plasma levels.
  
  
  CONCLUSIONS
  Subcutaneous immunization with hsp65-alum protects Apoe⁻/⁻ mice against progression of early atherosclerosis. Administration of anti-CD45RB antibody provided no incremental benefit to the athero-protective effects of hsp65-alum treatment alone.
authors.affiliation: Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Hospital, L8:03, SE-17176 Stockholm, Sweden.
authors.forename: Roland
authors.initials: R
authors.lastname: Klingenberg
authors.forename: Daniel F J
authors.initials: DF
authors.lastname: Ketelhuth
authors.forename: Daniela
authors.initials: D
authors.lastname: Strodthoff
authors.forename: Silvia
authors.initials: S
authors.lastname: Gregori
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology*; D006937:Hypercholesterolemia / Q000276:immunology / Q000628:therapy; D016233:Immunotherapy, Active; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018834:Chaperonin 60; D024101:Mitochondrial Proteins
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D006360:Heat-Shock Proteins; D017493:Leukocyte Common Antigens; C041524:aluminum sulfate; C557066:Hspd1 protein, mouse; D018834:Chaperonin 60; D024101:Mitochondrial Proteins