BEHAVIORAL & PHYSIOLOGICAL CONSEQUENCES OF LOSS

早期的社会创伤在行为和生理上都会影响到发育中的个体。随着青少年人群中艾滋病毒感染率的上升，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。由于对HIV感染者疾病发展的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是当务之急。研究表明，将非人类灵长类动物婴儿与其母亲分开一小段时间会导致免疫系统发生永久性变化。这些药物具有增强的天然细胞毒性。尚未确定的是，这些变化是否有害，即导致感染后疾病风险增加或疾病进程迅速进展。在这项研究中，我们评估了20只四岁尾辫猕猴接种SIVsmE660后的疾病进展。其中一半的动物将在六个月大时经历为期两周的母体分离，另一半将成为来自同一社会群体的未被分离的配对对照组。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育都有很好的记录。感染前后的全血细胞计数、分类和流式细胞仪将用于确定淋巴细胞总数和比例以及淋巴细胞亚群(CD4+、CD8+、CD20+和CD16+)。还将监测对两种肿瘤细胞系(K562和Raji)的自然细胞毒性。感染后，所有人的血液将通过全病毒酶联免疫吸附试验和聚合酶链式反应检测抗体和病毒水平。还将收集所有受试者的定量行为观察。感染10个月后，动物将被处死，并检查组织的病理变化。到目前为止，已有一只动物从丹佛抵达，并已完成检疫。这只动物将在六周内感染SIVsmE660病毒。另有四只动物计划在今年春天初抵达。

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.