Cyclosporine immunosuppression does not prevent the production of donor-specific antibody capable of mediating allograft vasculopathy

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Alison GareauTimothy D G Lee

Abstract

Late cardiac graft rejection, primarily mediated by allograft vasculopathy (AV), remains a major limitation to cardiac transplantation, even in the face of significant calcineurin inhibitor (CNI) immunosuppression. The role played by alloantibody in AV is unclear. Evidence that CNI immunosuppression suppresses CD4(+) T-cell function would suggest that antibody production and effector function would be severely limited in CNI-treated patients. In this study we examine the capacity of CNI-treated animals to develop effective alloantibody that can mediate AV. Wild-type (WT) B6 mice were alloimmunized using donor splenocytes or a fully major histocompatibility complex-mismatched allogeneic abdominal aortic graft in the presence of CNI immunosuppression (30 or 50 mg/kg/day cyclosporine A). Anti-serum was harvested and tested using complement-dependent in vitro cytotoxicity assays. Anti-serum was passively transferred to immunodeficient RAG1(-/-) recipients of allogeneic grafts. C4d deposition was quantified in the allografts from WT recipients. CNI immunosuppression did not prevent the development of alloantibody in response to either immunization method (p < 0.05). Passive transfer of anti-serum generated AV lesions in immunodefici...Continue Reading

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Citations

Feb 19, 2013·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Melvin SoCamille L Hancock Friesen

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