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 该项目的重点是检查这种下降的原因(S)在 分子水平。我们已经证明，激活是通过 老年人淋巴细胞植物血凝素的研究 如~3H-胸腺嘧啶核苷降低所显示的个体受损 掺入，并降低其合成和mRNA表达 IL-2及其受体(IL-2R)。对该计划的评估 联合用药对T细胞活化参数的影响 佛波酯PMA和钙离子载体A23187揭示 老年人再次表现出较低的~3H-胸腺嘧啶核苷 但对IL-2的表达无明显影响 或IL-2R。PHA是一种有丝分裂原，通过 抗原的T细胞受体，而PMA和A23187则绕过 表面受体。因此，我们的发现表明，IL-1的缺陷 2和IL-2R在老年人中的表达相关 随着细胞表面抗原受体复合体的改变 而不是IL-2和IL-2R基因座缺陷或 监管要素。此外，这些结果表明， 除IL-2和IL-2表达降低外的其他因素 2R是导致肿瘤细胞增殖能力减弱的原因 淋巴细胞被认为是衰老的一种功能。

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. We have shown that activation by phytohaemagglutinin (PHA) of human lymphocytes from aged individuals is impaired as demonstrated by lower 3H-thymidine incorporation, and decreased synthesis and mRNA expression of interleukin 2 (IL-2) and its receptor (IL-2R). Assessment of the same parameters of T cell activation using combined treatment with the phorbol ester PMA and the calcium ionophore A23187 revealed that elderly individuals again displayed lower 3H-thymidine incorporation but showed no impairment in the expression of IL-2 or IL-2R. PHA is a mitogen which acts nonspecifically through the T cell receptor for antigen, while PMA and A23187 bypass the surface receptor. Thus our findings suggest that the defect in IL- 2 and IL-2R expression seen in elderly individuals is associated with alterations in the cell surface antigen receptor complex rather than with a defect in the IL-2 and IL-2R gene loci or regulatory elements. Furthermore, these results indicate that additional factors other than decreased expression of IL-2 and IL- 2R are responsible the diminished proliferative capacity of lymphocytes seen as a function of aging.