MOLECULAR BASIS FOR DECEASED IMMUNE FUNCTION IN AGING HUMANS AND RATS

从人类和动物的研究中可以很好地确定 随着年龄增长而出现的免疫功能的普遍下降。 这个项目的重点是检查这种下降的原因(S)在 分子水平。特别是，我们关注的是 有丝分裂原对T淋巴细胞的激活作用三种T细胞蛋白 到目前为止已经检查过的有：白细胞介素2(IL-2)，一种淋巴因子 对某些T细胞的增殖是绝对必要的 白介素2受体(IL-2R)，细胞表面受体 以及干扰素-γ，另一种淋巴因子，其调节 与IL-2密切相关。白介素2和白介素2R的表达 检测了人外周血淋巴细胞(PBL)的基因 形成13名年轻捐赠者和17名老年捐赠者。除了减少 增殖能力，老年个体表现出显著的 IL-2蛋白活性和蛋白表达的降低 IL-2R相对年轻个体。这些下降是 伴有IL-2和IL-2R特异性水平下降 MRNA.干扰素a也得到了类似的结果。 伽玛在较小数量的捐赠者中。因此，看起来 这三个基因对抗原的诱导作用都降低了 刺激导致观察到的T细胞功能减弱 在老年人身上。

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.