HELPER T LYMPHOCYTE FUNCTION IN VITAMIN A DEFICIENCY

维生素 A 缺乏症中的辅助 T 淋巴细胞功能

• 批准号: 3142037
• 负责人: COLLEEN Elizabeth HAYES
• 金额: $ 11.64万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3142037
• 关键词: B lymphocyte; T cell receptor; biological signal transduction; cyclic AMP; helper T lymphocyte; immunoglobulin E; interleukin 2; interleukin 4; interleukin 5; laboratory mouse; leukocyte activation /transformation; macrophage; protein biosynthesis; retinoate; vitamin A deficiency

Vitamin A is essential for many biological functions. The close relationship between vitamin A and immunity is particularly significant for human health. Mildly A-deficient children die of infections at up to 12 times the rate of well-nourished children. Supplementary vitamin A reduces the incidence of cancer and infectious disease. Vitamin A-deficiency has a striking effect on antibody responses; IgG responses decrease by 80% compared to controls at a stage in A-deficiency when IgM responses are unaffected. This immune response defect is attributable to helper T lymphocytes. The A- deficient T cells sense foreign antigen, but do not signal 8 cells to grow and produce IgG. This block is fully reversed in vitro by retinyl acetate. The molecular basis for the helper T cell functional block in vitamin A-deficient animals is completely unknown. We formulated two hypotheses to explain this defect. Our results are consistent with a type-2 helper T cell failure to transduce activation signals, or with retinoid control over interleukin gene expression. Experiments are proposed to define the molecular basis for the vitamin A-dependence of T cells. Signal transduction through T cell antigen receptor molecules and through accessory molecules in A-deficient (A-) and A-sufficient (A+) T cells will be analyzed. B cell stimulatory lymphokine production by A+ and A- T cells will be quantitated with and without added vitamin A. If signal transduction is normal, but lymphokine production is decreased, lymphokine mRNA steady state levels will be determined, and if different, transcript initiation rates studied. In addition, evidence for a nuclear retinoid receptor will be sought. Finally, retinoids will be tested in vitro and in vivo for their ability to sustain the immune response. This research will describe the molecular basis for the retinoid dependence of helper T lymphocyte function. It will also contribute to a model for the vitamin's role in cell growth and differentiation, generally. Finally, it will provide insight into the relationship between retinoids, infectious disease, and possibly cancer.

维生素A是许多生物功能所必需的。收盘 维生素A与免疫之间的关系尤其重要 对人类健康意义重大。轻度A缺乏症儿童死于 感染率高达营养良好儿童的12倍。 补充维生素A可降低癌症发病率和 传染病。 维生素A缺乏对抗体反应有显著影响； 与对照组相比，免疫球蛋白应答在一个阶段下降了80% 当IgM反应不受影响时，A缺乏症。这种免疫力 应答缺陷可归因于辅助性T淋巴细胞。A- 缺陷T细胞感知外来抗原，但不向8细胞发出信号 培养和生产免疫球蛋白。这种阻滞剂在体外可被完全逆转 维甲酸乙酯。 辅助性T细胞功能阻断的分子基础 缺乏维生素A的动物是完全未知的。我们制定了 解释这一缺陷的两个假设。我们的结果是一致的 2型辅助性T细胞无法转导激活 信号，或类维甲酸对白介素类基因表达的控制。 建议用实验来定义分子基础。 维生素A--T细胞的依赖性。 通过T细胞抗原受体分子的信号转导和 通过A-亏(A-)中的辅助分子和A-充分 (a+)T细胞将被分析。B细胞刺激淋巴因子 A+和A-T细胞的产量将用和 没有添加维生素A，如果信号转导正常，但 淋巴因子产生减少，淋巴因子mRNA处于稳定状态 将确定级别，如果不同，还将启动文字记录 所研究的利率。此外，核类维甲酸的证据 将寻找受体。最后，维甲酸将在 在体外和体内维持免疫反应的能力。 这项研究将描述维甲酸的分子基础。 辅助性T淋巴细胞功能的依赖性。它还将 为维生素在细胞生长中的作用提供一个模型 一般而言，是差异化。最后，它将提供对 维甲酸与感染性疾病和 可能是癌症。