BEHAVIORAL & PHYSIOLOGICAL CONSEQUENCES OF LOSS

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• 批准号: 6116361
• 负责人: JULIE M WORLEIN
• 金额: $ 8.67万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116361
• 关键词: AIDS; Mammalia; Primates; animal tissue; hematology; immunology; infection; inflammation; lymphatic system; psychology; virus

Early social traumas affect the developing individual both behaviorally and physiologically. As the incidence of HIV infection rises in adolescent populations, particularly those with numerous childhood traumas, an understanding of the impact of these events on disease resistance becomes increasingly important. Since studies of disease progression in HIV-infected humans are often confounded by factors such as drug use, it is imperative to develop a nonhuman primate model that can eliminate these influences. It has been shown that separating nonhuman primate infants from their mothers for a short period of time results in permanent alterations in the immune system. These take the form of enhanced natural cytotoxicity. What has not been determined is whether these changes are detrimental, i.e., result in increased risk for disease or rapid progression of the disease process following infection. In this study we are evaluating disease progression following inoculation with SIVsmE660 in 20 four-year-old pigtailed macaques. Half of the animals will have experienced a two-week maternal separation at six months of age and half will be matched controls from the same social group that have not been separated. The subjects have been part of an experimental protocol at the University of Colorado Health Sciences Center and their behavioral and immune development is well documented. Complete blood counts, differentials and flow cytometry before and after infection will be used to determine total numbers and proportions of lymphocytes as well as lymphocyte subsets (CD4+, CD8+, CD20+ and CD16+). Natural cytotoxicity to two tumor cell lines (K562 and Raji) will also be monitored. After infection, blood of all individuals will be examined for levels of antibody and virus by whole-virus enzyme-linked immunosorbent assay and polymerase chain reaction. Quantitative behavioral observations will also be collected on all subjects. Ten months after infection animals will be sacrificed and tissues examined for pathological changes. To date, one animal has arrived from Denver and has completed quarantine. This animal will be infected with SIVsmE660 in six weeks. Four more animals are scheduled to arrive early this spring.

早期的社会创伤会影响发育中个体的行为和生理。 随着青少年群体中艾滋病毒感染率的上升，特别是那些有大量童年创伤的青少年，了解这些事件对疾病抵抗力的影响变得越来越重要。 由于对艾滋病毒感染者疾病进展的研究经常受到药物使用等因素的干扰，因此必须开发一种可以消除这些影响的非人类灵长类动物模型。 研究表明，将非人类灵长类婴儿与母亲短暂分开会导致免疫系统发生永久性改变。这些采取增强的天然细胞毒性的形式。 尚未确定的是这些变化是否有害，即导致疾病风险增加或感染后疾病过程快速进展。 在这项研究中，我们正在评估 20 只四岁猪尾猕猴接种 SIVsmE660 后的疾病进展。 一半的动物将在六个月大时经历为期两周的母亲分离，一半将与来自同一社会群体但尚未分离的对照动物配对。 这些受试者是科罗拉多大学健康科学中心实验方案的一部分，他们的行为和免疫发展都有详细记录。 感染前后的全血细胞计数、分类和流式细胞术将用于确定淋巴细胞以及淋巴细胞亚群（CD4+、CD8+、CD20+和CD16+）的总数和比例。 还将监测对两种肿瘤细胞系（K562 和 Raji）的天然细胞毒性。 感染后，将通过全病毒酶联免疫吸附测定和聚合酶链反应检查所有个体的血液中的抗体和病毒水平。 还将收集所有受试者的定量行为观察结果。 感染后十个月，将处死动物并检查组织的病理变化。 迄今为止，一只动物已从丹佛抵达并已完成检疫。 该动物将在六周内感染 SIVsmE660。 另外四只动物计划于今年春天早些时候抵达。