REGULATION BY NATURAL KILLER CELLS

体内自然杀伤(NK)细胞活性的选择性操纵将是 用于确定NK细胞在以下方面的重要性：(1) 移植抵抗肿瘤；(2)原发肿瘤形成；(3) 正常骨髓干细胞功能的调节。NK敏感或 将从体内使用的肿瘤细胞系中选择耐药变体 选择方案或体外诱导分化的受控方法。 NK溶血易感性的这种变异性的潜在基础 将会被分析。 体内NK活性的调节将使用遗传变异来产生 在服用SELECT后天然NK活性有明确的变化 体内免疫血清。将完成肿瘤细胞的移植 人NK细胞体外相对敏感性与NK细胞水平的相关性 各自肿瘤受者的活体情况。原发肿瘤的发生将 使用化学或病毒制剂在患有SELECT的小鼠身上进行 免疫系统的缺陷。骨髓干细胞数量将是 使用体外集落生长系统进行计算。我们将选择变种 使用对照方法根据NK敏感性检测肿瘤细胞 肿瘤细胞分化后的体外分化 与NK易感性的变化平行。克隆体内的细胞 显示分化改变的形态标志的同一肿瘤系 将进行NK分析。 NK细胞代表一种细胞类型，具有有趣的特性，使其成为 某些类型的恶性细胞和正常细胞的调控候选 活着。本研究应有助于更深入地理解 初发期NK细胞的生理学及其在体内的潜在作用 肿瘤的发生，以及对骨髓干细胞可能的调节作用 细胞。(Sr)

Select manipulation of natural killer (NK) cell activity in vivo will be used to establish the importance of NK cells in relation to: (1) transplantation resistance against tumors; (2) primary oncogenesis; and (3) regulation of normal bone marrow stem cell function. NK-sensitive or -resistant variants will be selected from tumor cell lines using in vivo selection protocols or controlled induction of differentiation in vitro. The underlying basis for this variability of susceptibility to NK lysis will be analyzed. Regulation of NK activity in vivo will be produced using genetic variants with defined variations in innate NK activity after administering select immune sera in vivo. Transplantatlon of tumor cells will be done correlating the relative NK susceptibility in vitro to the NK levels in vivo of the recipients of the respective tumors. Primary oncogenesis will be carried out using chemical or viral agents in mice with select deficiencies in the immune system. Bone marrow stem cell numbers will be calculated using in vitro colony growth systems. We will select variants of tumor cells according to NK susceptibility using controlled differentiation in vitro of tumor cells following differentiation in parallel to variations in NK susceptibility. Cloning of cells within the same tumor line displaying morphological markers of changed differentiation will be carried out for NK analysis. NK cells represent one cell type with interesting properties making it a candidate for regulation of certain types of malignant and normal cells in vivo. The present study should lead to a deeper understanding of the physiology of the NK cells and their potential roles in vivo during primary oncogenesis, as well as possible regulatory function as to bone marrow stem cells. (SR)