Aguila H L, Weissman I L
Department of Pathology Stanford University School of Medicine, CA. 94305, USA.
Blood. 1996 Feb 15;87(4):1225-31.
Bone marrow (BM) transplants from one individual to an irradiated histoincompatible individual of the same species are rejected. In mice, the primary host barrier cells that recognize bone marrow grafts bearing hematopoietic histocompatibility antigens bear surface markers of natural killer (NK) lymphocytes. Because of the innate ability of NK cells to kill susceptible targets, it has been proposed that the cytotoxic bone marrow graft rejection. To test this hypothesis, we purified hematopoietic stem cells from mice and incubated them with purified populations of actively cytotoxic allogeneic and semisyngeneic NK cells, followed by analysis of the ability of the treated hematopoietic stem cells (HSCs) to rescue lethally irradiated syngeneic animals. Such rescue was unimpaired. Also, HSC allografts were transplanted into transgenic mice deficient in NK and killer T-cell cytotoxicity generated by expressing diphtheria toxin A chain under the control of granzyme A promoter. Allogeneic HSCs were susceptible to allogeneic restriction in these mice, implying that the effector functions of NK marker-positive cells do not require NK cell cytotoxicity.
将一个个体的骨髓移植到同一物种受辐射的组织不相容个体中会被排斥。在小鼠中，识别携带造血组织相容性抗原的骨髓移植物的主要宿主屏障细胞带有自然杀伤（NK）淋巴细胞的表面标志物。由于NK细胞具有杀死易感靶标的先天能力，有人提出细胞毒性骨髓移植排斥反应。为了验证这一假设，我们从小鼠中纯化造血干细胞，并将它们与具有活性细胞毒性的同种异体和半同种异体NK细胞的纯化群体一起孵育，然后分析处理后的造血干细胞（HSC）拯救致死性照射的同基因动物的能力。这种拯救不受影响。此外，将HSC同种异体移植物移植到在颗粒酶A启动子控制下表达白喉毒素A链而缺乏NK和杀伤性T细胞细胞毒性的转基因小鼠中。在这些小鼠中，同种异体HSC易受同种异体限制，这意味着NK标志物阳性细胞的效应功能不需要NK细胞的细胞毒性。
