NK CELL ROLE IN RESISTANCE TO LEUKEMIA

这项提案的总体目标是研究自然杀伤（NK）细胞的功能。 在白血病过程中的作用，以及它们对白血病的调节活性。 人类正常造血细胞的增殖和分化。 具体来说，我们计划研究外周血NK细胞抗白血病 正常供体和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， 体外白血病细胞生长的克隆形成试验，和（2）抗 在单细胞测定中， 51铬释放测定和竞争性抑制测定。 我们将 进一步探讨白血病细胞分期与白血病细胞分化程度的关系 分化（通过形态学，表型细胞化学， 和细胞遗传学标准）和它们对NK细胞攻击的敏感性。的 还将研究NK细胞抗白血病反应性的机制。 将检测内源性和活化NK细胞。NK细胞将在 主要由白细胞介素-2和各种干扰素激活。 我们还将研究克隆的NK细胞（或细胞毒性因子） 从这些细胞）从正常供体和白血病患者来介导 抗白血病作用 由于白血病是造血系统的疾病，NK细胞已经被广泛应用于治疗白血病。 显示对造血发挥调节作用，因此必须 研究NK细胞生长调节功能的机制， 正常造血祖细胞的分化。 NK细胞的作用 将研究对以下造血祖细胞的影响：GM-CFC，BFU-E， 和GMME-CFC。 这些研究可能提供了深入了解的机制失调， 白血病造血，并可能导致新的协议的发展 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)