IMMUNE FUNCTION AND BIODEFENSE IN CHILDREN, ELDERLY, AND COMPROMISED POPULATIONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 感染西尼罗河病毒(WNV)的脑炎风险随着年龄的增长而急剧增加。患有神经侵袭性疾病的人，如果在70岁以下，死亡率不到4%，之后死亡率上升到20%以上。我们在ONPRC的合作者用两剂病毒(1 x 107或1 x 109 pfu/动物)挑战了16岁恒河猴(17-30岁)和9只成年恒河猴(6-9岁)；一些实验包括从TNPRC昆虫中产生的蚊子唾液腺提取物(SGE)。此外，15只食蟹猴在胸腺切除和/或CD8 T细胞耗尽后接受挑战，以测试不同程度的免疫缺陷。动物在临床上保持正常。未检测到可归因于西尼罗河病毒感染的发烧、食欲变化或行为。全血定量聚合酶链式反应显示离散的、短暂的病毒血症；然而，从未分离出传染性病毒。对先天免疫反应的分析显示，在感染后第2至10天，单核细胞和嗜酸性粒细胞(伴有SGE)显著增加。此外，流式细胞术分析显示CD3-细胞的增殖增加。在获得性免疫方面，发现与年龄相关的CD4+T细胞增殖减少。几乎所有动物都产生了体液反应，并被检测到。结果表明，非人类灵长类动物对西尼罗河病毒的攻击具有有效的先天防御能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Risk of encephalitis from West Nile virus (WNV) infection increases dramatically with age. Individuals suffering neuroinvasive illness have mortality rates of less than 4% if under the age of 70, after which rates rise to over 20%. Our collaborators at ONPRC challenged sixteen age rhesus macagues (17-30 yrs) and 9 adult Rhesus (6-9 yrs) with two does of virus (1 x 107 or 1 x 109 pfu/animal); some experiments included mosquito salivary gland extract (SGE) generated from the insectory at TNPRC. Additionally fifteen Cynomolgus monkeys were challenged after thymectomy and/or CD8 T cell depletion to test various levels of immunodeficiency. Animals remained clinically normal. No fever, change in appetite, or behavior was detected that could be attributed to WNV infection. Quantitative PCR of whole blood revealed discrete and short lived viremia; however infectious virus was never isolated. Analysis of innate immune response revealed a marked increase in monocytes and eosinophils (with SGE) between days 2 and 10 post infection. Additionally flow cytometric analysis of PBMC revealed increased proliferation of CD3- cells. With regard to adaptive immunity, an age-associated reduction in CD4+ T cell proliferation was found. Humoral responses developed and were detected in nearly all animals. The results suggest that non-human primates mount and maintain an effective innate defense to WNV challenge.