ASSESSMENT OF SIV+ CD4-LOW MANGABEYS

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。 在人类感染艾滋病毒和猕猴感染猴免疫缺陷病毒(SIV)的情况下，CD4+T细胞耗尽与疾病进展加速之间的联系已经得到很好的证实。在我们的研究之前，我们观察到SIV在其自然灵长类宿主(即乌贼)中的感染导致接近正常水平的CD4+T细胞，尽管其血浆病毒载量相似。 在2000年和2006年从SIV+芒果鼠中转移血浆后，5只芒果鸟的CD4+T细胞水平下降到血液中低于100个细胞/微升，这在淋巴结中也可以观察到。在过去的9年里，这些水平一直保持在18到100个细胞/微升的血液中。在耶克斯群体中，存在定义SIV+芒果鸟体内CD4+T细胞水平的应该是艾滋病的情况并不常见(在筛查的105只SIV+芒果鸟中，只有4只是CD4低)。 我们最近测试了这五(5)名CD4-低SIV+芒果鼠对流感疫苗的反应能力。我们给他们接种了两次疫苗，并将血浆送到疾控中心进行分析，以量化流感特异性抗体的水平。通过微量中和试验和血凝抑制试验，确定所有5只曼加比都能对流感疫苗产生有效的抗体反应，即使在非常低的CD4+T细胞水平上也是如此。 我们现在正在评估这些芒果的各种T细胞亚群，以确定这些亚群中的哪些可能在这些SIV+CD4-低芒果中发挥T辅助细胞的作用。到目前为止，研究人员已经确定CD3+/CD4-/CD8-(双阴性)T细胞是最有可能的候选细胞。

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. The association between CD4+ T-cell depletion and an accelerated rate of disease progression is well established for HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques. Prior to our studies, SIV infection in its natural primate host (i.e. sooty mangabeys) was observed to result in near normal levels of CD4+ T-cells despite similar plasma viral loads. Following transfer of plasma from an SIV+ mangabeys in 2000, and 2006, five mangabeys exhibited a decline in CD4+ T cell levels to below 100 cells/ul of blood which is also be observed in lymph nodes. These levels have remained between 18 and 100 cells/ul of blood for the past 9 years. The presence of what should be AIDS defining CD4+ T-cell levels in SIV+ mangabeys is an uncommon occurrence within the Yerkes colony (only four of the 105 SIV+ mangabeys screened are CD4-low). We recently tested the ability of these five (5) CD4-low SIV+ mangabeys to respond to an influenza vaccination. We vaccinated them twice and sent the plasma to the CDC for analysis to quantify the levels of influenza specific antibodies. Through microneutralization assays and hemaglutination inhibition it was determined that all five mangabeys were able to mount effective antibody responses to the influenza vaccination, even with the very low levels of CD4+ T cells. We are now assessing the various T cell subsets in these mangabeys to determine which of these subsets could potentially be fulfilling the T helper cell role in these SIV+ CD4-low mangabeys. Efforts thus far have identified the CD3+/CD4-/CD8- (double-negative) T cells as the most likely candidate.