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Simultaneous Transplantation of Hematopoietic Stem Cells and a Vascularized Composite Allograft Leads to Tolerance

2014; Wolters Kluwer; Volume: 98; Issue: 2 Linguagem: Inglês

10.1097/tp.0000000000000204

1534-6080

David W. Mathes, Jeff Chang, Billanna Hwang, Scott S. Graves, Barry E. Storer, Tiffany Butts-Miwongtum, George E. Sale, Rainer Storb,

Nerve injury and regeneration

We have previously demonstrated that tolerance to a vascularized composite allograft (VCA) can be achieved after the establishment of mixed chimerism. We test the hypothesis that tolerance to a VCA in our dog leukocyte antigen-matched canine model is not dependent on the previous establishment of mixed chimerism and can be induced coincident with hematopoietic cell transplantation (HCT).Eight dog leukocyte antigen-matched, minor antigen mismatched dogs received 200 cGy of radiation and a VCA transplant. Four dogs received donor bone marrow at the time of VCA transplantation (group 1), whereas a second group of four dogs did not (group 2). All recipients received a limited course of postgrafting immunosuppression. All dogs that received HCT and VCA were given donor, third-party, and autologous skin grafts.All group 1 recipients were tolerant to their VCA (>62 weeks). Three of the four dogs in group 2 rejected their VCA transplants after the cessation of immunosuppression. Biopsies obtained from the muscle and skin of VCA from group 1 showed few infiltrating cells compared with extensive infiltrates in biopsies of VCA from group 2. Compared with autologous skin and muscle, elevated levels of CD3+ FoxP3+ T-regulatory cells were found in the skin and muscle obtained from the VCA of HCT recipients. All group 1 animals were tolerant to their donor skin graft and promptly rejected the third-party skin grafts.These data demonstrated that donor-specific tolerance to all components of the VCA can be established through simultaneous nonmyeloablative allogeneic HCT and VCA transplantation protocol.