HELPER T LYMPHOCYTE FUNCTION IN VITAMIN A DEFICIENCY

维生素A对许多生物功能至关重要。 收盘 维生素A与免疫力的关系 对人类健康意义重大。 轻度A缺乏的儿童死于 感染率是营养良好儿童的12倍。 补充维生素A可以降低癌症的发病率， 传染病 维生素A缺乏对抗体反应有显著影响; IgG应答在一个阶段与对照相比降低80%， IgM反应不受影响的A缺乏症。 这种免疫 应答缺陷可归因于辅助性T淋巴细胞。 A- 缺陷型T细胞可感知外源抗原，但不向8细胞发出信号 生长并产生IgG 这种阻断在体外被完全逆转， 乙酸视黄酯 辅助性T细胞功能阻滞的分子基础 缺乏维生素A的动物是完全未知的。 我们制定 有两个假设来解释这个缺陷。 我们的研究结果是一致 2型辅助性T细胞无法激活 信号，或与类维生素A控制白细胞介素基因的表达。 实验提出了定义的分子基础， T细胞的维生素A依赖性。 通过T细胞抗原受体分子的信号转导和 通过辅助分子在A-缺乏（A-）和A-充足 将分析（A+）T细胞。 B细胞刺激性淋巴因子 A+和A-T细胞的产生将用和 不添加维生素A。 如果信号传导正常， 淋巴因子产生减少，淋巴因子mRNA稳态 水平将被确定，如果不同，转录起始 率研究。 此外，核维甲酸的证据 将寻求接收器。 最后，类维生素A将在 它们在体外和体内维持免疫应答的能力。 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 有助于维生素在细胞生长中的作用的模型， 差异化，一般来说。 最后，它将提供洞察力， 类维生素A、传染病和 可能是癌症

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.