Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection.

ABSTRACT: Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models. Live imaging revealed that DSAs were sequestrated in the circulation of the recipients and failed to reach the endocrine cells of grafted islets. We used murine heart transplantation models to confirm that endothelial cells were the only accessibl

SUBMITTER: Chen CC 

PROVIDER: S-EPMC5749508 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature