Hamby K, Trexler A, Pearson T C, Larsen C P, Rigby M R, Kean L S
The Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
Am J Transplant. 2007 Aug;7(8):1884-96. doi: 10.1111/j.1600-6143.2007.01864.x.
We have used a sensitive and specific in vivo killing assay to monitor the kinetics, anatomic location and mechanisms controlling NK-mediated rejection of Balb/c bone marrow by C57BL/6 natural killer (NK) cells. We find that NK killing of fully allogeneic bone marrow is a rapid, highly efficient process, leading to substantial rejection of transplanted marrow within 6 h of transplant and elimination of 85% of the transplanted cells within 2 days. NK-mediated rejection occurred predominantly in the spleen, with sparing of rejection in the bone marrow and lymph nodes. Rejection was dependent on Perforin gene function, but was independent of interferon-gamma. Finally, rejection of Balb/c bone marrow by B6 NK cells required signaling through the Ly49D receptor, but occurred despite blockade of NKG2D, which distinguishes these results from previous studies using semiallogeneic transplant pairs. These results identify NK cells as highly active mediators of bone marrow rejection, and suggest that inhibiting NK function early during transplantation may increase the efficiency of engraftment and allow successful engraftment of limiting doses of donor bone marrow.
我们使用了一种灵敏且特异的体内杀伤试验来监测动力学、解剖位置以及控制C57BL/6自然杀伤（NK）细胞介导的对Balb/c骨髓排斥反应的机制。我们发现，NK细胞对完全异基因骨髓的杀伤是一个快速、高效的过程，导致移植后6小时内移植骨髓大量排斥，且2天内85%的移植细胞被清除。NK细胞介导的排斥反应主要发生在脾脏，骨髓和淋巴结中的排斥反应较少。排斥反应依赖穿孔素基因功能，但不依赖于干扰素-γ。最后，B6 NK细胞对Balb/c骨髓的排斥需要通过Ly49D受体进行信号传导，但尽管阻断了NKG2D仍会发生排斥反应，这使得这些结果与之前使用半异基因移植对的研究有所不同。这些结果表明NK细胞是骨髓排斥反应的高活性介质，并提示在移植早期抑制NK功能可能会提高植入效率，并使有限剂量的供体骨髓成功植入。
