Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys

J Clin Invest. 2010 Apr;120(4):1275-84. doi: 10.1172/JCI41861. Epub 2010 Mar 24.


Chronic rejection currently limits the long-term efficacy of clinical transplantation. Although B cells have recently been shown to play a pivotal role in the induction of alloimmunity and are being targeted in other transplant contexts, the efficacy of preemptive B cell depletion to modulate alloimmunity or attenuate cardiac allograft vasculopathy (CAV) (classic chronic rejection lesions found in transplanted hearts) in a translational model has not previously been described. We report here that the CD20-specific antibody (alphaCD20) rituximab depleted CD20+ B cells in peripheral blood, secondary lymphoid organs, and the graft in cynomolgus monkey recipients of heterotopic cardiac allografts. Furthermore, CD20+ B cell depletion therapy combined with the calcineurin inhibitor cyclosporine A (CsA) prolonged median primary graft survival relative to treatment with alphaCD20 or CsA alone. In animals treated with both alphaCD20 and CsA that achieved efficient B cell depletion, alloantibody production was substantially inhibited and the CAV severity score was markedly reduced. We conclude therefore that efficient preemptive depletion of CD20+ B cells is effective in a preclinical model to modulate pathogenic alloimmunity and to attenuate chronic rejection when used in conjunction with a conventional clinical immunosuppressant. This study suggests that use of this treatment combination may improve the efficacy of transplantation in the clinic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / analysis
  • Antigens, CD20 / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Complement Activation
  • Cyclosporine / therapeutic use*
  • Female
  • Gene Expression
  • Graft Rejection / prevention & control*
  • Graft Survival
  • Immunosuppressive Agents / therapeutic use*
  • Isoantibodies / immunology
  • Lymphocyte Depletion*
  • Macaca fascicularis
  • Male
  • Myocardium / pathology*
  • Rituximab
  • T-Lymphocytes / metabolism
  • Transplantation, Homologous


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Immunosuppressive Agents
  • Isoantibodies
  • Rituximab
  • Cyclosporine