Scientific article

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

Publication date2020

Intraportal islet transplantation is plagued by an acute destruction of transplanted islets. Amongst the first responders, NK cells and macrophages harbour 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 analyse the impact of antibody-induced NKG2D blockade in islet transplantation. NKG2D-ligand expression was analysed in rat and human islets. Syngeneic marginal mass intraportal 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.

  • NKG2D
  • hypersensitivity type II
  • islet transplantation
  • liver
  • Swiss National Science Foundation - P00P3_165837/1
Citation (ISO format)
DELAUNE, Vaihere et al. Antibody-induced NKG2D blockade in a rat model of intraportal islet transplantation leads to a deleterious reaction. In: Transplant International, 2020. doi: 10.1111/tri.13589
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Article (Published version)
ISSN of the journal0934-0874

Technical informations

Creation04/16/2020 12:27:00 PM
First validation04/16/2020 12:27:00 PM
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