NKG2D Blockade Significantly Attenuates Ischemia-Reperfusion Injury in a Cardiac Transplantation Model

BackgroundNKG2D (natural killer group 2 member D), are activating or coactivating receptor on NK cells, γδ T, and CD8+ T cells, stimulates cytokine secretion by the former two and plays a costimulatory role for the last CD8+ T cells.MethodsMale Lewis rat hearts were flushed and stored in cold Bretschneider preservation solution for 8 hours. Anti-NKG2D monoclonal antibody (mAb) was administered before transplantation into syngeneic recipients. Expressions of Troponin-T, myeloperoxidase (MPO), tumor necrosis factor (INF), (ICAM) and interleukin (IL)-17 were examined on days 1, 3, and 7 after reperfusion.ResultsWe observed that isografts from anti-NKG2D mAb-treated animals showed decreased cardiac troponin-T, low expression of MPO, TNF, and ICAM, and superior cardiac output. Furthermore, blockade of NKG2D significantly reduced the number of γδ T cells, which are the main source of IL-17 production.ConclusionBlockade of NKG2D significantly attenuated ischemia-reperfusion injury in a cardiac transplantation model. The effect coincided with a low expression of TNFα, ICAM and a reduced number of infiltrating IL-17–producing γδ T cells.