Subcutaneous immunization with heat shock protein-65 reduces atherosclerosis in Apoe -/- mice

Roland Klingenberg, Daniel F J Ketelhuth, Daniela Strodthoff, Silvia Gregori, Göran K. Hansson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)540-547
Number of pages8
JournalImmunobiology
Volume217
Issue number5
DOIs
Publication statusPublished - May 2012

Keywords

  • Atherosclerosis
  • Immune system
  • Immunomodulation
  • Leukocytes
  • Vascular biology

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology

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