Presensitization Accelerates Antibody-Mediated Rejection in Mouse Intestinal Transplantation.

Abstract

INTRODUCTION: The presence of donor-specific antibodies (DSAs) is a risk factor for antibody-mediated rejection (AMR) in the context of organ transplantation. However, the mechanisms and clinical characteristics of AMR in intestinal transplantation remain poorly understood, largely due to a lack of suitable animal models. In the present study, we performed intestinal transplantation in presensitized murine recipients as a model of AMR to better understand how this phenomenon contributes to graft rejection. METHODS: Skin from donor B6 mice was grafted onto the backs of recipient C3H mice. The presensitized C3H mice then received intestinal allografts from B6 mice 14 ds later. The presensitized and nonsensitized mice were compared in terms of their circulating DSAs levels and their intestinal allograft characteristics at various time points. RESULTS: Flow cytometric analysis showed that circulating DSA levels increased over time in the presensitized recipients. Moreover, the presensitized recipients exhibited more severe intestinal graft rejection at day 4 post-transplantation than the nonsensitized mice. Although immunostaining revealed no significant difference in the numbers of infiltrating CD4and CD8cells between the groups post-transplantation, the numbers of infiltrating CD20and CD68cells were significantly higher in the presensitized recipients. Furthermore, C3 and C4 deposition on the microvascular endothelium of intestinal allografts and capillaritis were observed after transplantation. CONCLUSIONS: We successfully established a presensitized mouse model of AMR in the context of intestinal transplantation. Our model will be valuable in elucidating the mechanisms underlying AMR and exploring strategies for managing this phenomenon to improve the outcomes of intestinal transplantation.