Date: Saturday, June 11, 2016
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Halls C&D
[Background] Reconstructive transplantation represents a valid therapeutic option after devastating tissue loss. Routine clinical application, however, is hampered by the toxicity of long-term maintenance immunosuppression. The current study investigated a novel short-term immunomodulatory strategy in a murine hind limb transplantation model.
[Methods] Fully MHC-mismatched allogeneic, orthotopic hind limb transplants were performed from Balb/C to C57BL/6 mice. Recipient animals in the experimental groups received no treatment (Group 1); 0.25mg CTLA4 Ig on postoperative days (POD) 0, and 0.25mg on POD 2, 4, and 6 (Group 2); 20mg/kg anti-T cells (anti-Thy 1.2 mAb) on POD-1 plus CTLA4-Ig and 1mg/kg Rapamycin (POD0-9) (Group 3). Flow cytometric analysis was performed to evaluate mixed chimerism and clonal deletion of alloreactive T cells.
[Results] CTLA4 Ig treated group showed increased graft survival compared to the non-treated controls. Combination of T cell depletion and CTLA4-Ig plus short-course of Rapamycin increased VCA survival significantly (MST 105 days; p<0.01). Mixed chimerism was detected in recipients receiving the combined treatment protocol with 5.013 ± 1.23 % of donor derived CD11b+ cells on POD 55. Vβ – TCR staining profiles in recipients after full treatment showed 1.570 ± 0.3700 % of [nu]β5+CD4+ T cells, while naïve C57BL/6 express 3.567 ± 0.3690 % of [nu]β5+CD4+ T cells, suggesting the actuation of central deletion of developing donor-reactive T cells. Graft-Infiltrating Foxp3+ regulatory T cells of donor origin were significantly increased on POD 30 and 60 suggesting an important regulatory role exerted by donor Treg cells.
[Conclusion] This study shows that the combination of T cell depletion, costimulation blockade, and a short-course of Rapamycin prevents VCA rejection and significantly prolongs graft survival without the need for myeloablative conditioning or toxic maintenance immunosuppression.
CITATION INFORMATION: Oh B, Furtmüller G, Fryer M, Akre P, Cooney D, Lee W, Raimondi G, Brandacher G. Peritransplant Costimulation Blockade Combined with a Short-Course of Rapamycin Prevents Rejection of Vascularized Composite Allografts. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Oh B, Furtmüller G, Fryer M, Akre P, Cooney D, Lee W, Raimondi G, Brandacher G. Peritransplant Costimulation Blockade Combined with a Short-Course of Rapamycin Prevents Rejection of Vascularized Composite Allografts. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/peritransplant-costimulation-blockade-combined-with-a-short-course-of-rapamycin-prevents-rejection-of-vascularized-composite-allografts/. Accessed December 5, 2020.
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