Antibody‐induced NKG2D blockade in a rat model of intraportal islet transplantation leads to a deleterious reaction

Vaihere Delaune, Christian Toso, Arianna Kahler‐Quesada, Florence Slits, Quentin Gex, Gürkan Kaya, Vanessa Lavallard, Lorenzo Annibale Orci, Andrea Peloso, Stéphanie Lacotte
2020 Transplant International  
Intraportal islet transplantation is plagued by an acute destruction of transplanted islets. Amongst the first responders, NK cells and macrophages harbor an activating receptor, NKG2D, recognizing ligands expressed by stressed cells. We aimed to determine whether islet NKG2D ligand expression increases with culture time, and to analyze the impact of antibody-induced NKG2D blockade in islet transplantation. NKG2D-ligand expression was analyzed in rat and human islets. Syngeneic marginal mass
more » ... raportal islet transplantations were performed in rats: control group, recipients transplanted with NKG2D-recombinant-treated islets (recombinant group), and recipients treated with a mouse anti-rat anti-NKG2D antibody and transplanted with recombinant-treated islets (antibody-recombinant group). Islets demonstrated increased gene expression of NKG2D ligands with culture time. Blockade of NKG2D on NK cells decreased in vitro cytotoxicity against islets. Recipients from the control and recombinant groups showed similar metabolic results; conversely, treatment with the antibody resulted in lower diabetes reversal. The antibody depleted circulating and liver NK cells in recipients, who displayed increased macrophage infiltration of recipient origin around the transplanted islets. In vitro blockade of NKG2D ligands had no impact on early graft function. Systemic treatment of recipients with an anti-NKG2D antibody was deleterious to the islet graft, possibly through an antibody-dependent cell-mediated cytotoxicity reaction.
doi:10.1111/tri.13589 pmid:32003082 fatcat:r4djkcsw45e6vnfe36p26cdaze