Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background: The interspecies incompatibility of CD47 is an important mechanism triggering rejection of cellular xenografts, including both hematopoietic and non-hematopoietic cells, by recipient macrophages. Our recent studies showed that intrasplenic transplantation of CD47-deficient hepatocytes into syngeneic wild-type (WT) mice induces rapid innate immune cell activation and expansion (with >90% of WBCs expressing Mac-1 by day 3), and the associated graft loss. However, it remains unknown as to the role of donor CD47 in the regulation of donor-specific T cell responses following hepatocyte transplantation. Here, we addressed this question by assessing ovalbumin (OVA)-specific responses in WT mice following hepatocyte transplantation from WT or CD47-deficient donors. Methods: B6 mice received intrasplenic transplantation of hepatocytes from WT or CD47-/- OVA+ B6 donors, or sham operation (controls) 7 days prior to WT OVA+ B6 mouse skin grafting. Donor skin graft survival and mixed lymphocyte reaction (MLR) were evaluated to assess donor antigen (OVA)-specific T cell responses. Result: All sham-operated controls rejected OVA+ skin grafts between 19 and 25 days, with a median survival time of 21 days. Compared to the control recipients, intrasplenic transplantation of CD47 -/- OVA+ hepatocytes resulted in significant (p<0.0001) acceleration of donor skin graft rejection. In contrast, mice receiving WT OVA+ hepatocytes had prolonged, rather than accelerated survival of donor OVA+ skin grafts. Consistently, T (both CD4 and CD8) cells from mice receiving CD47 -/-, but not WT, OVA+ hepatocytes showed a significantly enhanced proliferative responses to OVA+ stimulators in comparison with those from sham-operated controls (p<0.05), whereas T cells from all 3 groups showed comparable proliferation in response to 3rd-party allogeneic stimulators. Conclusion: CD47 on donor hepatocytes plays an important role in the control of donor antigen-specific T cell responses. Further investigation of the mechanistic link between the enhanced anti-donor T cell responses and the early innate immune cell activation resulting from lacking CD47-SIRPa signaling following CD47 -/- hepatocyte transplantation will help determine the possibility of CD47 incompatibility to stimulate anti-donor T cell responses after xenotransplantation.
To cite this abstract in AMA style:Zhang M, Wang H, Navarro-Alvarez N, Zheng Y, Yang Y-G. Donor CD47 Plays a Critical Role in the Control of Alloreactive T Cell Activation Following Hepatocyte Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-cd47-plays-a-critical-role-in-the-control-of-alloreactive-t-cell-activation-following-hepatocyte-transplantation/. Accessed November 24, 2020.
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