Long-Lasting Skin Allograft Tolerance Induced and Maintained by Short-Term Vascularized Bone Marrow Transplant in a Mouse Model.

C.-H. Lin,¹ M. Anggelia,¹ H.-Y. Cheng,¹ Y.-L. Wang,¹ W.-Y. Chuang,¹ C.-H. Lin,¹ G. Brandacher.²

¹Center for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
²Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.

Meeting: 2016 American Transplant Congress

Abstract number: 374

Keywords: Bone marrow transplantation, Co-stimulation, Mixed chimerism, Tolerance

Session Information

Session Name: Concurrent Session: Allograft Tolerance 2: Animal Models

Session Type: Concurrent Session

Date: Tuesday, June 14, 2016

Session Time: 2:30pm-4:00pm

Presentation Time: 3:18pm-3:30pm

Location: Room 309

Background: Accumulating evidences indicate that vascularized bone marrow transplantation (VBMT) plays a critical role in inducing tolerance of vascularized composite allografts (VCA). Recipients with long-term surviving allografts show a higher degree of cell trafficking between donor and recipient. We hypothesize that short-term existence of VBMT may promote engraftment the donor cells and induce allograft tolerance.

Methods: Osteomyocutaneous (OMC) allografts from Balb/c were transplanted onto C57BL/6 mice and 1 mg anti-CD154 (POD 0), 0.5 mg CTLA4Ig (POD 2), and 3mg/kg/day for 7 days every other day for 3 weeks of rapamycin were administered. Transplanted mice combined with skin graft were divided into 4 groups: Group 1, OMC + skin graft (n=4); Group 2, OMC removed at POD 30 + skin graft (n=4); Group 3, OMC removed at POD 60 + skin graft (n=4); Group 4, OMC removed at POD 120 + skin graft (n=4).

Results: Sixteen of 20 mice receiving OMC allografts achieved long-term graft survival (>120 days). In animals with long-term allograft survival, peripheral blood analysis showed that cellular and humoral responses (IgG and IgM) were abrogated and proinflammatory cytokines (IL-17A, IFNγ, TNFα, CD40L) were suppressed. Peripheral and central tolerance were showed by a significant deletion of Vb5⁺ CD4⁺ cells in peripheral blood and thymus in tolerated allograft animals, but not in rejected mice (p<0.05). Interestingly, transplanted animals which OMC allografts were removed at POD 30 were able to achieve long-term skin allograft survival with (>60 days). It was consistent with the data that showed animals before OMC removed versus after OMC removed showed no significantly elevated immune response. Using Rag2^-/- mice, OMC allograft was able to delayed skin graft rejection after 5×10⁶ CD4⁺T cell donor specific injection (n=2, MST=33.5).

Conclusions:Efficacy of VBMT to promote long-term allograft survival has been shown in this study. The data also suggest that intra- and extrathymic clonal deletion is one of mechanisms contribute to maintenance of tolerance.

CITATION INFORMATION: Lin C.-H, Anggelia M, Cheng H.-Y, Wang Y.-L, Chuang W.-Y, Lin C.-H, Brandacher G. Long-Lasting Skin Allograft Tolerance Induced and Maintained by Short-Term Vascularized Bone Marrow Transplant in a Mouse Model. Am J Transplant. 2016;16 (suppl 3).

To cite this abstract in AMA style:

Lin C-H, Anggelia M, Cheng H-Y, Wang Y-L, Chuang W-Y, Lin C-H, Brandacher G. Long-Lasting Skin Allograft Tolerance Induced and Maintained by Short-Term Vascularized Bone Marrow Transplant in a Mouse Model. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/long-lasting-skin-allograft-tolerance-induced-and-maintained-by-short-term-vascularized-bone-marrow-transplant-in-a-mouse-model/. Accessed November 25, 2024.

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