MOLECULAR BASIS FOR DECEASED IMMUNE FUNCTION IN AGING HUMANS AND RATS

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。 这 该项目的重点是审查这一下降的原因， 分子水平。 我们已经证明， 老年人淋巴细胞植物血凝素（PHA） 3 H-胸苷水平降低证明个体受损 掺入，并减少合成和mRNA表达 白细胞介素2（IL-2）及其受体（IL-2 R）。 评估 T细胞活化的相同参数，使用与 佛波醇酯PMA和钙离子载体A23187显示 老年人再次显示出较低的3 H-胸苷 但在IL-2的表达中没有显示出损害 或IL-2 R。 PHA是一种有丝分裂原，其通过 T细胞抗原受体，而PMA和A23187绕过T细胞抗原受体。 表面受体 因此，我们的研究结果表明，在IL- 2和IL-2 R的表达在老年人中观察到， 细胞表面抗原受体复合物的改变 而不是IL-2和IL-2 R基因座缺陷，或 监管要素。 此外，这些结果表明， 除了IL-2和IL-10表达降低之外， 2 R是导致细胞增殖能力下降的原因。 淋巴细胞被视为衰老的函数。

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.