Hematopoietic stem cells are not direct cytotoxic targets of natural killer cells
Hematopoietic stem cells are not direct cytotoxic targets of natural killer cells
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DOI：
10.1182/blood.v87.4.1225.bloodjournal8741225
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发表时间：
1996-02-15
期刊：
影响因子：
20.3
通讯作者：
Weissman, IL
中科院分区：
文献类型：
--
作者：
Aguila, HL;Weissman, IL
骨髓（BM）移植从一个人到同一物种的辐射组织不相容的个人被拒绝。在小鼠中，识别带有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）淋巴细胞的表面标记。由于NK细胞具有杀死易感靶点的先天能力，因此已经提出NK细胞的细胞毒性功能是骨髓移植排斥反应的负责介质。为了验证这一假设，我们从小鼠中纯化了造血干细胞，并将其与纯化的具有细胞毒性的同种异体和半同基因NK细胞群一起孵育，然后分析经处理的造血干细胞（HSC）拯救致死性辐照的同基因动物的能力。这样的救援没有受到影响。此外，将HSC同种异体移植物移植到NK和杀伤T细胞毒性缺陷的转基因小鼠中，所述NK和杀伤T细胞毒性是通过在颗粒酶A启动子的控制下表达白喉毒素A链产生的。在这些小鼠中，同种异体HSC对同种异体限制敏感，这意味着NK标记阳性细胞的效应功能不需要NK细胞的细胞毒性。(C)1996年，美国血液学会。
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 suceptible targets, it has been proposed that the cytotoxic functions of NK cells are the responsible mediators of bone marrow graft rejection. To test this hypothesis, we purified hematopoietic stem cells from mice and incubated them with purified populations of actively cytotoxic allegeneic 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. (C) 1996 by The American Society of Hematology.