AGE-ASSOCIATED ALTERATIONS IN HUMAN NK CELL SYSTEM

人类 NK 细胞系统中与年龄相关的变化

• 批准号: 3116455
• 负责人: RAJABATHER KRISHNARAJ
• 金额: $ 8.5万
• 依托单位: EVANSTON HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3116455
• 关键词: adenosine triphosphate; aging; antiantibody; cell biology; cell population study; cytogenetics; cytotoxicity; human age group; human middle age (35-64); human old age (65+); immunofluorescence technique; immunopharmacology; interferons; lymphocyte; mathematical model; monoclonal antibody; neoplasm /cancer immunology; radiotracer; single cell analysis; spectrometry; surface antigens

Alterations in the Natural Killer (NK) cell system in healthy humans will be investigated in a comprehensive cross-sectional study with special reference to aging. In view of the elevated incidence of neoplasia in the elderly, it is important to learn about the NK cell biology in healthy aged humans. Studies by others on this subject have been very limited, performed on impure cell preparations employing a single, conventional semi-quantitative assay and yielded conflicting results. The multi-technique approach used in our preliminary studies have revealed that the healthy elderly (greater than 80 yr) represent a homogeneous group, expressing an average peripheral blood NK cell activity higher than that of younger adults (20-40 yr). We propose to investigate the alterations in the NK cell frequency and expression by performing cytolytic funtional assays, kinetic analysis of tumor target lysis, surface phenotype (N-901, Leu-7 and Leu-11a) determination, differential sensitivity to ATP (a negative modulator of NK activity), and interferon as well as and an assessment of the critical steps in NK cytolysis (target binding, frequency of active NK cells and recycling capacity) by using a single-cell assay on semi-solid matrix. Highly enriched large granular lymphocytes from 300 healthy volunteers (20-100 yrs) will be utilized. Correlations will be sought between the NK cell surface marker expression and many of the cytolytic steps that may distinguish the individuals in the intra- and inter-age groups. Influence of age on the NK cell recycling capacity and its interacting ability with tumor targets will be examined. We will also examine the cause(s) for an elevated maximal cytotoxic potential (Vmax) exhibited by the elderly (greater than 80 yr). We will determine if the NK activity per cell or NK cell frequency goes up with age. Furthermore, based on a proposition that the higher level of NK activity in the greater than 80 yr old humans may be attributable to a deletion of a population of younger individuals with lower NK activity, a late-life (greater than 70 yr) longitudinal study will be initiated. Accomplishment of these objectives might reveal if the critical cytolytic steps that distinguish the low and high NK activity of young adults are the same that separate the younger from the elderly NK cell features, helping to elucidate age-associated modulations. It is also hoped that the results might form a basis for future pharmacological interventions.

健康人的自然杀手（NK）细胞系统的改变将 在一项特殊的综合横断面研究中进行调查 参考衰老。 鉴于肿瘤的发病率升高 老年人，了解健康老化的NK细胞生物学很重要 人类。 其他人对这个主题的研究非常有限， 在不纯净的细胞制剂上使用单一的常规细胞制剂进行 半定量测定法，并产生矛盾的结果。 这 我们的初步研究中使用的多技术方法表明 健康的老年人（大于80岁）代表一个同质群体， 表达平均外围血液NK细胞活性高于 年轻人（20 - 40年）。 我们建议调查 NK细胞频率和表达通过执行细胞溶解功能 测定，肿瘤靶裂解的动力学分析，表面表型（N-901， LEU-7和LEU-11A）确定，对ATP的差异敏感性（A NK活动的负调节剂）和干扰素以及 评估NK细胞溶解的关键步骤（靶标的，频率 通过使用单细胞测定法 半固体矩阵。 来自300的高度富集的大颗粒淋巴细胞 健康的志愿者（20 - 100年）将被使用。 相关性是 在NK细胞表面标记表达和许多 细胞溶解步骤可能会区分个体内和内部的个体 年龄组。 年龄对NK细胞回收能力的影响和 将检查其与肿瘤靶标的相互作用能力。 我们也会 检查原因是否具有升高的最大细胞毒性（VMAX） 由老年人展出（大于80岁）。 我们将确定NK是否 每个细胞或NK细胞频率随着年龄的增长而增加。 此外， 基于一个主张，即更高的NK活性较高 超过80岁的老人可能归因于删除人口 NK活动较低的年轻人（大于70岁） 纵向研究将开始。 完成这些 目标可能会揭示是否区分的关键细胞溶解步骤 年轻人的低和高NK活动与分开 年轻的NK细胞特征年轻，有助于阐明 与年龄相关的调制。 还希望结果可能会形成 未来药理干预措施的基础。