NK CELL ROLE IN RESISTANCE TO LEUKEMIA

这项提议的总体目标是研究自然杀伤(NK)细胞。 在白血病病程中的作用及其调节活性 人正常造血细胞的增殖和分化。 具体地说，我们计划研究外周血NK细胞抗白血病 正常献血者和活动性白血病患者的反应性 缓解：(1)新鲜来源的克隆性白血病细胞 白血病细胞体外生长的克隆形成试验，以及(2)抗 单细胞检测中白血病细胞的异质性群体， 51铬释放试验和竞争抑制试验。我们会 进一步探讨白血病细胞分期与临床分期的关系 分化(由形态、表型细胞化学、 和细胞遗传学标准)以及它们对NK细胞攻击的敏感性。这个 此外，还将对S的NK细胞抗白血病活性机制进行研究。 将对内源性和激活的NK细胞进行测试。自然杀伤细胞将是 主要由白介素2和各种干扰素激活。 我们还将研究克隆的NK细胞(或细胞毒因子)的作用 从这些细胞中)从正常供者和白血病患者 抗白血病作用。 由于白血病是一种造血系统疾病，NK细胞一直以来 显示对造血起调节作用的，是势在必行 研究NK细胞对生长和生长的调节作用机制 正常造血祖细胞的分化。自然杀伤细胞的作用 将对以下造血祖细胞进行研究：GM-CFC，BFU-E， 和GMME-cfc。 这些研究可能为深入了解失控的机制提供帮助。 白血病中的造血，并可能导致新方案的开发 用于治疗白血病患者。(IS)

The overall aim of this proposal is to study natural killer (NK) cells' role in the course of leukemic disease, and their regulatory activity over proliferation and differentiation of normal hemopoietic cells in man. Specifically, we plan to investigate peripheral blood NK-cell anti-leukemia reactivity of normal donors and leukemic patients with active disease and in remission against: (1) freshly derived clonogenic leukemia cells in clonogenic assay for leukemic cell growth in vitro, and (2) against heterogeneous population of leukemia cells in a single cell assay, 51chromium-release assay, and competitive inhibition assay. We will further investigate the relationship between the stage of leukemic cell differentiation (as determined by morphological, phenotypic cytochemical, and cytogenetic criteria) and their sensitivity to NK cell attack. The mechanism(s) of NK-cell anti-leukemia reactivity will be also studied. Endogenous and activated NK cells will be tested. NK cells will be activated primarily by interleukin-2 and various species of interferons. We will also study the effect of cloned NK cells (or the cytotoxic factor from these cells) from normal donors and patients with leukemia to mediate anti-leukemia effect. Since leukemia is a disease of hemopoietic system and NK cells have been shown to exert regulatory activities over hemopoiesis, it is imperative to study the mechanism of NK-cell regulatory functions over growth and differentiation of normal hemopoietic progenitors. The effect of NK cells on the following hemopoietic progenitors will be studied: GM-CFC, BFU-E, and GMME-CFC. These studies may provide insight into the mechanism of disregulation of hemopoiesis in leukemia, and may lead to the development of new protocols for treatment of leukemia-diseased patients. (IS)