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REGULATION BY NATURAL KILLER CELLS

自然杀伤细胞的调节

基本信息

批准号：
3167451
负责人：
ROLF KIESSLING
金额：
$ 11.5万
依托单位：
KAROLINSKA INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-01-01 至 1985-12-31
项目状态：
已结题

项目摘要

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)

体内自然杀伤 (NK) 细胞活性的选择操作将是用于确定 NK 细胞在以下方面的重要性：(1) 对肿瘤的移植抵抗； (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 -使用体内方法从肿瘤细胞系中选择耐药变体选择方案或体外受控分化诱导。 NK 裂解敏感性差异的根本原因将被分析。体内 NK 活性的调节将通过遗传变异产生施用 select 后先天 NK 活性有明确的变化体内免疫血清。将进行肿瘤细胞移植将体外相对 NK 敏感性与体内 NK 水平相关联各肿瘤受体的体内。原发性肿瘤发生将使用化学或病毒剂在小鼠身上进行选择免疫系统缺陷。骨髓干细胞数量将是使用体外菌落生长系统计算。我们将选择变体使用受控的方法根据 NK 敏感性对肿瘤细胞进行肿瘤细胞分化后的体外分化与 NK 敏感性的变化平行。内细胞的克隆显示分化改变的形态学标记的同一肿瘤系将进行NK分析。 NK 细胞代表一种具有有趣特性的细胞类型，使其成为调节某些类型的恶性和正常细胞的候选者体内。目前的研究应该可以使人们更深入地了解 NK 细胞的生理学及其在初级阶段体内的潜在作用肿瘤发生以及对骨髓干的可能调节功能细胞。 (SR)