CD45RB-targeting strategies for promoting long-term allograft survival and preventingchronic allograft vasculopathy1
M Sho, H Harada, DM Rothstein, MH Sayegh - Transplantation, 2003 - journals.lww.com
M Sho, H Harada, DM Rothstein, MH Sayegh
Transplantation, 2003•journals.lww.comBackground. CD45RB is a potent immunomodulatory target to achieve long-term allograft
survival. We evaluated the in vivo effect of anti-CD45RB monoclonal antibody (mAb)
treatment in combination with conventional immunosuppression or costimulatory blockade
strategies as a therapeutic modality for future clinical application. Methods. A fully MHC-
mismatched vascularized mouse cardiac allograft model was used to test the interactions
between anti-CD45RB mAb and conventional immunosuppressive drugs or costimulatory …
survival. We evaluated the in vivo effect of anti-CD45RB monoclonal antibody (mAb)
treatment in combination with conventional immunosuppression or costimulatory blockade
strategies as a therapeutic modality for future clinical application. Methods. A fully MHC-
mismatched vascularized mouse cardiac allograft model was used to test the interactions
between anti-CD45RB mAb and conventional immunosuppressive drugs or costimulatory …
Abstract
Background.
CD45RB is a potent immunomodulatory target to achieve long-term allograft survival. We evaluated the in vivo effect of anti-CD45RB monoclonal antibody (mAb) treatment in combination with conventional immunosuppression or costimulatory blockade strategies as a therapeutic modality for future clinical application.
Methods.
A fully MHC-mismatched vascularized mouse cardiac allograft model was used to test the interactions between anti-CD45RB mAb and conventional immunosuppressive drugs or costimulatory blockade of the CD40/CD154 or B7/CD28 pathway. Chronic rejection was examined histologically for development of chronic allograft vasculopathy.
Results.
Cyclosporine significantly abrogated the effect of anti-CD45RB therapy. In contrast, rapamycin acted synergistically with anti-CD45RB mAb in promoting long-term allograft survival. CD154 blockade further enhanced the tolerogenic efficacy of anti-CD45RB mAb. These synergistic effects of combination treatments also prevented the development of chronic allograft vasculopathy.
Conclusion.
CD45RB-targeting strategy in combination with the use of rapamycin or costimulatory blockade promotes allograft tolerance and prevents chronic rejection.
Lippincott Williams & Wilkins