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 language | English |
|---|---|
| Pages (from-to) | 540-547 |
| Number of pages | 8 |
| Journal | Immunobiology |
| Volume | 217 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2012 |
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Keywords
- Atherosclerosis
- Immune system
- Immunomodulation
- Leukocytes
- Vascular biology
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Hematology
Cite this
Subcutaneous immunization with heat shock protein-65 reduces atherosclerosis in Apoe -/- mice. / Klingenberg, Roland; Ketelhuth, Daniel F J; Strodthoff, Daniela; Gregori, Silvia; Hansson, Göran K.
In: Immunobiology, Vol. 217, No. 5, 05.2012, p. 540-547.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Subcutaneous immunization with heat shock protein-65 reduces atherosclerosis in Apoe -/- mice
AU - Klingenberg, Roland
AU - Ketelhuth, Daniel F J
AU - Strodthoff, Daniela
AU - Gregori, Silvia
AU - Hansson, Göran K.
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Immune system
KW - Immunomodulation
KW - Leukocytes
KW - Vascular biology
UR - http://www.scopus.com/inward/record.url?scp=84858797859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858797859&partnerID=8YFLogxK
U2 - 10.1016/j.imbio.2011.06.006
DO - 10.1016/j.imbio.2011.06.006
M3 - Article
C2 - 21798617
AN - SCOPUS:84858797859
VL - 217
SP - 540
EP - 547
JO - Immunobiology
JF - Immunobiology
SN - 0171-2985
IS - 5
ER -