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.
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.
Authors: T Zhang; S Fresnay; E Welty; N Sangrampurkar; E Rybak; H Zhou; X-F Cheng; Q Feng; C Avon; A Laaris; M Whitters; A M Nagelin; R M O'Hara; A M Azimzadeh Journal: Am J Transplant Date: 2011-07-12 Impact factor: 8.086
Authors: Silvia Gregori; Patrizia Mangia; Rosa Bacchetta; Eleonora Tresoldi; Frank Kolbinger; Catia Traversari; Josè M Carballido; Jan E de Vries; Ulf Korthäuer; Maria-Grazia Roncarolo Journal: J Exp Med Date: 2005-04-18 Impact factor: 14.307