REGULATION BY NATURAL KILLER CELLS

选择性操纵体内自然杀伤（NK）细胞活性， 用于确定NK细胞在以下方面的重要性：（1） 对肿瘤的移植抗性;（2）原发性肿瘤发生;和（3） 调节正常骨髓干细胞功能。 NK敏感或 - 抗性变体将从肿瘤细胞系中选择，使用体内 选择方案或体外受控诱导分化。 这种NK细胞溶解敏感性变异性的潜在基础 将被分析。 将使用遗传变异体产生体内NK活性的调节 在给予选择性的抗肿瘤药物后， 体内免疫血清。 肿瘤细胞的移植将被完成 将体外相对NK易感性与体内NK水平相关联， 在各自肿瘤的受体体内。 原发性肿瘤将 使用化学或病毒试剂在具有选择性的小鼠中进行 免疫系统的缺陷。 骨髓干细胞数量将 使用体外菌落生长系统计算。 我们将选择变体 根据NK敏感性，使用对照 肿瘤细胞在体外的分化， 与NK易感性的变化平行。 细胞内的克隆 显示分化改变的形态学标志物的相同肿瘤系 将进行NK分析。 NK细胞代表了一种具有有趣特性的细胞类型，使其成为一种 调节某些类型的恶性和正常细胞的候选者， vivo. 本研究应有助于更深入地了解 NK细胞的生理学及其在原发性肝癌中的潜在作用 肿瘤发生以及对骨髓干细胞的可能调节功能 细胞 （斯洛伐克共和国）

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)