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: 3116447
• 负责人: RAJABATHER KRISHNARAJ
• 金额: $ 8.04万
• 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 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3116447
• 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.

健康人自然杀伤（NK）细胞系统的改变将 在一项全面的横断面研究中进行调查， 提到老化。 鉴于美国肿瘤发生率升高， 老年人，重要的是要了解健康老年人的NK细胞生物学 人类 其他人对这一问题的研究非常有限， 采用单一的常规方法对不纯的细胞制备物进行 半定量分析，并产生矛盾的结果。 的 在我们的初步研究中使用的多技术方法显示， 健康的老年人（大于80岁）代表同质组， 表达的平均外周血NK细胞活性高于 年轻人（20 - 40岁）。 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，肿瘤靶溶解的动力学分析，表面表型（N-901， Leu-7和Leu-11a）测定，对ATP（a）的不同敏感性 NK活性的负调节剂）和干扰素以及 评估NK细胞溶解的关键步骤（靶结合，频率 活性NK细胞和再循环能力）。 半固态基质 300例高度富集的大颗粒淋巴细胞 将使用健康志愿者（20 - 100岁）。 相关性将是 寻找NK细胞表面标志物表达和许多 细胞溶解步骤，可以区分内部和内部的个体， 跨年龄组。 年龄对NK细胞再循环能力的影响 将检测其与肿瘤靶点的相互作用能力。 我们还将 检查最大细胞毒性潜能（Vmax）升高的原因 老年人（大于80岁）。 我们将决定朝鲜是否 每个细胞的活性或NK细胞的频率随着年龄的增长而增加。 此外，委员会认为， 基于一个命题，即NK活性水平越高， 超过80岁的人可能归因于一个群体的缺失， NK活性较低的年轻个体，晚年（大于70岁） 将展开纵向研究。 完成这些 目的可能揭示，如果关键的细胞溶解步骤，区分 低和高NK活性的年轻的成年人是相同的，分开的， 年轻人从老年人NK细胞功能，有助于阐明 与年龄相关的调制。 也希望这些结果能形成一个 为今后的药物干预奠定基础。