EVIDENCE FOR A SIMILAR OR COMMON MECHANISM FOR NATURAL KILLER CELL ACTIVITY AND RESISTANCE TO HEMATOPOIETIC GRAFTS
EVIDENCE FOR A SIMILAR OR COMMON MECHANISM FOR NATURAL KILLER CELL ACTIVITY AND RESISTANCE TO HEMATOPOIETIC GRAFTS
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DOI：
10.1002/eji.1830070915
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发表时间：
1977-01-01
影响因子：
5.4
通讯作者：
CUDKOWICZ, G
中科院分区：
文献类型：
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作者：
KIESSLING, R;HOCHMAN, PS;CUDKOWICZ, G
两种类型的主机反应，不需要在小鼠中的免疫接种，不介导的T [胸腺衍生]淋巴细胞进行了比较：电阻的照射和非照射F1杂交接受正常或恶性造血细胞（Hh系统）的父母移植，和自然杀伤细胞对小鼠淋巴瘤（NK系统）的活性。使用YAC-1淋巴瘤细胞作为靶标，在NK系统中研究了已知影响骨髓移植物抗性的6个自变量的作用。共有以下特性：在生命的第4周期间成熟;对急性全身照射的低敏感性;依赖于骨髓的完整性，如通过89 Sr处理的小鼠中降低的反应性所证明的;通过单次注射抗巨噬细胞剂二氧化硅和γ来抑制。角叉菜胶;和通过多次注射亲本脾细胞到F1小鼠中的抑制。这些正相关性特别重要，因为大多数变量对传统免疫力有相反的影响或没有影响。F1代小鼠对亲本骨髓移植物特异性无反应，保留了NK细胞活性，遗传易感小鼠在NK细胞方面表现出低反应性，表明YAC-1和Hh-1不相容靶点的特异性不同。这种惊人的相似性极不可能是偶然的。在2种细胞介导的天然反应性中，一种非常相似或更可能是共同的机制起作用：NK和Hh系统中的效应细胞不携带B[骨髓来源]或T淋巴细胞标志物，但具有特异性。它们在体内的生成（可能是通过成熟或募集）依赖于与非淋巴辅助细胞的相互作用，这些辅助细胞不具有特异性，也能够在体外与Thy-1阳性F1杂交前杀伤细胞相互作用，这些细胞对亲本靶点具有特异性。由于胸腺在体内的独立性和对造血系统靶细胞的明显限制，这些反应性应有效地调节造血和监测白血病的发生。
Two types of host reactivities not requiring immunization in the mouse and not mediated by T [thymus derived] lymphocytes were compared: resistance of irradiated and nonirradiated F1 hybrids to accept parental grafts of normal or malignant hemopoietic cells (Hh system), and the natural killer cell activity against mouse lymphomas (NK system). The effects of 6 independent variables known to influence resistance to marrow grafts were investigated in the NK system using YAC-1 lymphoma cells as targets. The following properties were shared: maturation during the 4th wk of life; low sensitivity to acute total body irradiation; dependence on the integrity of bone marrow as demonstrated by reduced reactivity in 89Sr-treated mice; suppression by a single injection of the anti-macrophage agents silica and .iota. carrageenan; and suppression by multiple injections of parental spleen cells into F1 mice. These positive correlations are particularly significant because most of the variables have either opposing or no effect on conventional immunity. F1 mice rendered specifically unresponsive to parental marrow grafts retained NK cell activity, and genetically susceptible mice were rendered hyporeactive in terms of NK cells, indicating that the specificities of YAC-1 and Hh-1 incompatible targets were different. It is extremely unlikely that this remarkable parallelism is fortuitous. A very similar, or more likely a common mechanism, is operative in the 2 cell-mediated natural reactivities: effector cells in the NK and Hh systems do not bear B[bone marrow derived] or T lymphocyte markers but are endowed with specificity. They are dependent for generation in vivo (presumably by maturation or by recruitment) on the interaction with nonlymphoid accessory cells not endowed with specificity, capable of also interacting in vitro with Thy-1-positive F1 hybrid prekiller cells specific for parental targets. Because of thymus independence in vivo and apparent restriction to target cells of the hemopoietic system, these reactivities should be effective in the regulation of hemopoiesis and surveillance over leukemogenesis.