MOLECULAR BASIS FOR DECEASED IMMUNE FUNCTION IN AGING HUMANS AND RATS

衰老人类和大鼠免疫功能死亡的分子基础

• 批准号: 3821514
• 负责人: N J HOLBROOK
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 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/3821514
• 关键词: T lymphocyte; acquired immunodeficiency; aging; blood donor; gene expression; human subject; immune response genes; interferons; interleukin 2; leukocyte activation /transformation; messenger RNA; molecular genetics; molecular pathology

It is well established from human and animal studies that there is a general decrease in immune function that occurs with aging. This project focuses on examining the cause(s) for this decline at the molecular level. In particular, we have focused on the activation of T lymphocytes by mitogen. Three T-cell proteins have been examined thus far: interleukin 2 (IL-2), a lymphokine absolutely required for the proliferation of certain T cell populations; IL-2 receptor (IL-2R), the cell surface receptor for IL-2; and interferon gamma, another lymphokine whose regulation is intimately linked to IL-2. Expression of the IL-2 and IL-2R genes in human peripheral blood lymphocytes (PBL) was examined form 13 young and 17 elderly donors. In addition to decreased proliferative capacity, elderly individuals displayed a significant decrease in the amount of IL-2 protein activity and expression of IL-2R relative to younger individuals. These decrease were accompanied by decreased levels of IL-2 and IL-2R specific mRNA. Similar results have been obtained with interferon a gamma in a smaller number of donors. Thus, it appears that decreased induction of all three of these genes upon antigenic stimulation contributes to the diminished T cell function observed in the elderly.

从人类和动物研究中已经很好地确定， 随着年龄的增长，免疫功能普遍下降。 本项目的重点是研究这种下降的原因， 分子水平。 特别是，我们着重于 有丝分裂原激活T淋巴细胞。 三种T细胞蛋白 白细胞介素2（IL-2），一种淋巴因子， 是某些T细胞增殖所必需的 IL-2受体（IL-2 R），细胞表面受体， IL-2和干扰素γ，另一种淋巴因子，其调节 与IL-2密切相关。 IL-2和IL-2 R的表达 检测人外周血淋巴细胞（PBL）中的基因 13名年轻人和17名老年人。 除了减少 增殖能力，老年人表现出显着的 IL-2蛋白活性和表达量的降低 IL-2 R相对于年轻人。 这些减少是 伴有IL-2和IL-2 R特异性 mRNA。 用干扰素a也得到了类似的结果 在少数捐赠者中进行。 因此，似乎 降低所有这三种基因对抗原性 刺激有助于观察到的T细胞功能减弱 在老年人中。