Costimulatory Blockade in Combination with Donor Bone Marrow Infusion Induces Immune Tolerance Across A Full MHC Barrier In A Translational Large Animal Vascularized Composite Allotransplantation Model
Angelo A Leto Barone, Z. Ibrahim, G. Furtmüller, K. Sarhane, Yongchun Wang, Devin Miller, Madeline L. Fryer, Mohammed Alrakan, K. Sarkar, J. Shores, S. Bonawitz, C. Gordon, J. Sacks, G. Raimondi, D. Cooney, Zhaoli Sun, W. Lee, G. Brandacher
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引用次数: 1
Abstract
Fully MHCand gender mismatched MGH miniature swine underwent heterotopic hind-limb transplantation. Recipient animals received a short course of tacrolimus monotherapy, C/¡ donor BM infusion (60x10cells/kg), and CTLA4Ig (abatacept). Short course tacrolimus only and untreated animals served as controls. Chimerism was assessed by SRY-gene PCR analysis. Alloreactivity against donor antigens was assessed in vitro using CFSE-based Mixed Lymphocyte Reaction (CFSE-MLR) assays. Robust immune tolerance in vivo was assessed by secondary skin grafting. Tolerance maintenance upon allograft removal was tested in vitro by CFSE-MLR. Donor-specific antibodies (DSA) production was assessed using flow cytometry. Results
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