REGULATION IN E COLI EXTENDED TO LYMPHOMAS

该项目的长期目标是进一步提高 了解T细胞功能的调节。 两制 本研究将探讨：（1）糖皮质激素对基因表达的影响 小鼠T淋巴瘤中的表达;（2）基因的结构 编码人纤连蛋白的α和β亚基 受体及其在人T细胞系和其它细胞中调节 类型 糖皮质激素对免疫系统的多重作用， 动物和人，是他们广泛的临床基础。 使用. 从淋巴瘤或白血病建立的T细胞系具有 一直在研究糖皮质激素诱导的T细胞溶解， 小鼠胸腺瘤细胞系W7。 这种反应的机制 是模糊的，没有淋巴细胞特异性基因的调节， 糖皮质激素尚未被鉴定。 第一个目标是 项目是分离和表征cDNA克隆相应的 糖皮质激素（单独或与 cAMP）。 在初步实验中，我们有 成功地用消减杂交方法分离出 这样的cDNA克隆。 这些克隆体将被进一步鉴定 通过Southern和北方印迹分析。 的表达 相应的基因将在T淋巴瘤变异体和 不同的细胞类型 插入片段将被测序并进行基因组分析 克隆将被分离以分析调节的机制， 糖皮质激素对这些基因的影响 细胞表面纤连蛋白受体表达在一个亚群上， T淋巴细胞 这种受体介导的各种影响 纤连蛋白，特别是细胞粘附。 几种激素和 已经显示因子调节该受体的表达 各种细胞类型。 这种刺激可以引导交通 循环T淋巴细胞通过结缔组织到淋巴 器官或部位的炎症，或其迁移期间 发展 因此，这些受体可能在 在免疫反应中。 该项目的第二个目标是 分析编码α和β亚基的基因， 受体及其调控。 将分离基因组克隆， 这些基因的特征和调控由几种激素 并将对这些因素进行审查。 人T细胞系将用作 模型系统，以调查这种表达是否 受体受抗原激活调节，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.