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

Background. NKG2D (natural killer group 2 member D), are activating or coactivating receptor on NK cells, gamma delta T, and CD8(+) T cells, stimulates cytokine secretion by the former two and plays a costimulatory role for the last CD8(+) T cells. Methods. Male 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. Results. We 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 gamma delta T cells, which are the main source of IL-17 production. Conclusion. Blockade of NKG2D significantly attenuated ischemia-reperfusion injury in a cardiac transplantation model. The effect coincided with a low expression of TNF alpha, ICAM and a reduced number of infiltrating IL-17-producing gamma delta T cells.