53 - Communication libre
Inflammation & transplantation
16 mai 2019, 10:15 - 11:45, Szenario 1, 5ème étage


NKG2D blockade in a syngeneic rat model of intraportal islet transplantation
V. Delaune, C. Toso, A. Kahler-Quesada, F. Slits, Q. Gex, V. Lavallard, L. A. Orci, A. Peloso, S. Lacotte, Presenter: V. Delaune (Genève)

Intraportal islet transplantation is plagued by an acute destruction of transplanted islets, mostly mediated by the instant blood-mediated inflammatory reaction (IBMIR), where NK cells and macrophages are amongst the first responders. These cells harbor an activating receptor, NKG2D, which recognizes ligands expressed by stressed cells. The aims of this study were to determine whether NKG2D ligand expression increased in islets with culture time, and to analyze the impact of NKG2D blockade in islet transplantation.
Hypoxia-related (Hif1a) and NKG2D-ligand gene expressions were analyzed 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).
Rat and human islets demonstrated increased gene expression of NKG2D ligands with culture time. In rats, this was linked with increased Hif1a expression. Recipients from the control and recombinant groups showed similar metabolic results. However, treatment with the anti-NKG2D antibody resulted in NK cell depletion and lower diabetes reversal.
Treatment of recipients with the anti-NKG2D antibody was deleterious to the islet graft. Further explorations are needed to determine whether this is due to the antibody, with potential immunoallergic mechanisms, or to NK cell depletion.
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