REGULATION OF NEOPLASTIC T-LYMPHOCYTE AND HEMATOPOIETIC CELL PROLIFERATION

肿瘤 T 淋巴细胞和造血细胞增殖的调节

• 批准号: 4692223
• 负责人: F W RUSCETTI
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4692223
• 关键词: Herpesvirus saimiri; T lymphocyte; cell growth regulation; clone cells; flow cytometry; glucocorticoids; hormone regulation /control mechanism; human T cell lymphotropic virus type 2; human tissue; immune adherence reaction; immunofluorescence technique; interleukin 2; leukocyte activation /transformation; mixed tissue /cell culture; monoclonal antibody; neoplasm /cancer immunology; neoplastic cell; neoplastic growth; phosphatidylinositols; protein kinase C; radiotracer; transforming virus; viral carcinogenesis

Binding of the regulatory peptide, interleukin-2 (IL-2), to its specific receptor is a prerequisite for activated T lymphocytes to grow. Deprivation of IL-2 from T-cells results in all the cells coming to rest in GO. Recombinant, purified IL-2 was used to identify biochemical parameters associated with stimulation of these resting T-cells into cell cycle progression. Calcium levels, measured spectrophotometrically using Quin-2 dye, were markedly increased within one minute. No increase was observed with a non-homologous ligand. Also, it was shown that IL-2 stimulates rapid turnover in the phosphoinositol pathway followed by hydrolysis of phosphoinositides. It has been recently demonstrated that IL-2 binding produces a rapid and transient redistribution of protein kinase C (PK-C) from cytosol to cell membrane. This PK-C activity was correlated with the ability of T-cells to express T-cell receptors on their cell surface. Using radiolabeled IL-2 binding and cytofluorometric assays for anti-Tac, a monoclonal antibody to the IL-2 receptor, IL-2 was shown to stimulate increased IL-2 receptor expression on T-cells within 24 hrs. An increased level of IL-2 receptor became detectible by 4 hrs. Analysis of IL-2 receptor numbers after IL-2 stimulation showed major differences between IL-2 (6-9,000 per cell) and anti-Tac (35-45,000 per cell) binding. Resting, previously activated cells stimulated with phorbol esters have nearly equal numbers of binding sites with both ligands. Scatchard analysis of data reveals that the number of binding sites with high affinity (greater than 10-10M) correlated with IL-2 binding numbers and not with anti-Tac binding. Thus, IL-2 stimulation of T-cell growth results in an increased number of Tac antigen binding sites with lower affinity on the cell surface. Herpes-viruses, such as Herpesvirus saimiri (HVS), and RNA tumor viruses, such as Human T-cell leukemia virus (HTLV), can transform T-cells. Studies on metabolic events and IL-2 receptor regulation have shown major differences of growth control between normal and such transformed T-cells.

调节肽白细胞介素-2（IL-2）与其特异性结合 受体是活化的T淋巴细胞生长的先决条件。 从T细胞中去除IL-2导致所有细胞在体内休息。 走了 重组、纯化的IL-2用于鉴定生化参数 与刺激这些静止的T细胞进入细胞周期有关 进展 钙水平，使用Quin-2通过电化学计量法测量 染料，在一分钟内显著增加。 未观察到增加 与非同源配体结合 此外，研究表明，IL-2刺激 磷酸肌醇途径中的快速周转，随后水解 磷酸肌醇。 最近已经证明，IL-2结合 产生蛋白激酶C（PK-C）的快速和短暂的重新分布 从细胞质到细胞膜。 这种PK-C活性与 T细胞在其细胞表面表达T细胞受体的能力。 使用放射性标记的IL-2结合和细胞荧光测定抗Tac， IL-2受体的单克隆抗体，IL-2显示刺激 在24小时内增加T细胞上的IL-2受体表达。 增加 IL-2受体水平在4小时时变得可检测。 IL-2分析 IL-2刺激后的受体数量显示， IL-2（6- 9，000/细胞）和抗Tac（35- 45，000/细胞）结合。 静止的，先前用佛波醇酯刺激的活化细胞， 与两种配体的结合位点的数量几乎相等。 Scatchard 数据分析表明，高结合位点的数量 亲和力（大于10- 10 M）与IL-2结合数相关， 与抗Tac抗体结合 因此，IL-2刺激T细胞生长导致 增加的Tac抗原结合位点的数量， 细胞表面 疱疹病毒，如松鼠猴疱疹病毒（HVS）和RNA 肿瘤病毒，如人T细胞白血病病毒（HTLV），可以转化 T细胞 对代谢事件和IL-2受体调节的研究已经 显示出正常和这种生长控制之间的主要差异， 转化的T细胞