BEHAVIORAL & PHYSIOLOGICAL CONSEQUENCES OF LOSS

早期的社会创伤在行为和生理上都影响着个体的发展。随着青少年人群中艾滋病毒感染的发病率上升，特别是那些有许多童年创伤的青少年，了解这些事件对疾病抵抗力的影响变得越来越重要。由于艾滋病毒感染者的疾病进展研究经常受到药物使用等因素的干扰，因此开发一种能够消除这些影响的非人类灵长类动物模型势在必行。研究表明，将非人类灵长类动物的婴儿与母亲短暂分离会导致免疫系统的永久性改变。它们以增强天然细胞毒性的形式存在。尚未确定的是，这些变化是否有害，即是否导致疾病风险增加或感染后疾病进程的快速进展。在这项研究中，我们正在评估接种SIVsmE660后20只4岁长尾猕猴的疾病进展。一半的动物将在六个月大的时候经历两周的母亲分离，另一半将来自同一社会群体的匹配对照，但没有被分开。这些受试者是科罗拉多大学健康科学中心实验协议的一部分，他们的行为和免疫发育有很好的记录。感染前后采用全血细胞计数、差异和流式细胞术测定淋巴细胞总数和比例以及淋巴细胞亚群（CD4+、CD8+、CD20+和CD16+）。对两种肿瘤细胞系（K562和Raji）的天然细胞毒性也将进行监测。感染后，通过全病毒酶联免疫吸附试验和聚合酶链反应检测所有个体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10个月后处死动物，检查组织病理变化。迄今为止，一只动物已经从丹佛抵达并完成了检疫。这只动物将在六周内感染SIVsmE660。另外四只动物计划在今年早春到来。

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.