REGULATION IN E. COLI EXTENDED TO LYMPHOMAS

该项目的长期目标是获得更多 了解T细胞功能的调制。两种制度 将研究：(1)糖皮质激素对基因的影响 在小鼠T淋巴瘤中的表达；(2)基因结构 编码人纤维连接蛋白的α和β亚基 人T细胞系和其他细胞的受体及其调控 类型。 糖皮质激素对免疫系统的多重影响 动物和人类都是其广泛临床应用的基础 使用。从淋巴瘤或白血病建立的T细胞系 一直在研究糖皮质激素诱导的T细胞溶解，特别是 小鼠胸腺瘤细胞系W7。这种反应的机制 是不明确的，并且没有淋巴特异性基因受 糖皮质激素还没有被鉴定出来。这样做的第一个目的是 项目是分离和鉴定相应的cdna克隆 受糖皮质激素调节的基因(单独或与 CAMP)。在初步实验中，我们有 成功地使用消减杂交程序分离出 这样的cDNA克隆。这些其他克隆将进一步表征 经Southern和Northern杂交分析。的表达方式 相应的基因将在T淋巴瘤的变种和 不同的细胞类型。这些插入物将被测序并进行基因组分析 将分离克隆以分析其调控机制。 这些基因是由糖皮质激素引起的。 细胞表面纤维连接蛋白受体表达于 T淋巴细胞。这种受体介导的各种作用 纤维连接蛋白，特别是细胞黏附。几种激素和 已有研究表明多种因素可调节该受体的表达。 在各种类型的细胞上。这样的刺激可以引导交通 循环T淋巴细胞通过结缔组织到达淋巴组织 炎症的器官或部位，或它们在 发展。因此，这些受体可以发挥重要作用。 在免疫反应中。这个项目的第二个目标是 分析编码这个基因的阿尔法和贝塔亚基 受体及其调控。基因组克隆将被分离并 这些基因的特性及其受几种激素的调节 并将对各种因素进行审查。人类T细胞株将被用作 模型系统来调查这是否表达了 受体受抗原激活的调节，在T细胞 成熟。

The long-term objective of this project is to gain further understanding of the modulation of T-cell functions. Two systems will be investigated: (1) The effects of glucocorticoids on gene expression in murine T-lymphomas; (2) The structure of the genes encoding the alpha and beta subunits of the human fibronectin receptor and their regulation in human T-cell lines and other cell types. The multiple effects of glucocorticoids on the immune system, in both animals and man, are the basis for their extensive clinical use. T-cell lines established from lymphomas or leukemias have been to study glucocorticoid-induced T-cell lysis, in particular the murine thymoma cell line W7. The mechanism of this response is obscure, and no lymphoid-specific gene regulated by glucocorticoids has as yet been identified. The first aim of this project is to isolate and characterize cDNA clones corresponding to genes regulated by glucocorticoids (alone or in combination with cAMP) in W7 cells. In preliminary experiments, we have successfully used a subtractive hybridization procedure to isolate such cDNA clones. These other clones will be further characterized by Southern and Northern blot analyses. The expression of the corresponding genes will be examined in T-lymphoma variants and in different cell types. The inserts will be sequenced and genomic clones will be isolated to analyze the mechanisms of regulation of those genes by glucocorticoids. The cell surface fibronectin receptor is expressed on a subset of T-lymphocytes. This receptor mediates the various effects of fibronectin, and cell adhesion in particular. Several hormones and factors have been shown to modulate the expression of this receptor on various cell types. Such stimuli could direct the traffic of circulating T-lymphocytes through connective tissue to lymphoid organs or sites of inflammation, or their migration during development. Therefore, those receptors could play a major role in the immune response. The second aim of this project is to analyze the genes encoding the alpha and beta subunits of this receptor and their regulation. Genomic clones will be isolated and characterize and the regulation of these genes by several hormones and factors will be examined. Human T-cell lines will be used as model systems to investigate whether the expression of this receptor is modulated by antigenic activation and during T-cell maturation.