[摘要]：Background. Blockade of B7-CD28 interaction with CTLA4-Ig could prolong allograft survival in cardiac transplantation. NKG2D is an activating or coactivating receptor on NK cells, gamma delta T, and CD8(+) T cells and played an important role in transplant immunity. Methods. C57BL/6 (wild type and gamma delta(-/-) or interleukin (IL)-17(-/-)) mice were transplanted with allogeneic BALB/c hearts and treated with CTLA4-Ig alone or in combination with anti-NKG2D monoclonal antibodies. The survival of grafts was monitored daily by abdominal palpation until the complete cessation of cardiac contractility. Results. We found that wild type recipient treated with anti-NKG2D monoclonal antibodies plus CTLA4-Ig showed significantly prolonged survival cardiac allograft (> 90 days, P < 0.001). These in vivo results in combined therapy group correlated with low expression of interferon-gamma whereas increased expression of IL-4 and alternatively activated macrophage markers. Furthermore, with blockade of NKG2D, the number of IL-17-producing gamma delta T cells was significantly reduced, which was demonstrated as the main source of IL-17 production. And in our gamma delta(-/-) and IL-17(-/-) murine cardiac transplantation models, we found that gamma delta or IL-17 deficiency could significantly prolong cardiac allograft survival. Conclusion. Blockade of NKG2D is effective in synergizing with CTLA4-Ig to promote long-term cardiac allograft survival in mice, and this effect is associated with decreased infiltration of IL-17-producing gamma delta T cells.
