ASSESSMENT OF SIV+ CD4-LOW MANGABEYS

SIV CD4-低白眉猴的评估

• 批准号: 8172387
• 负责人: Donald L Sodora
• 金额: $ 3.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172387
• 关键词: Acquired Immunodeficiency Syndrome; Antibodies; Antibody Formation; Biological Assay; Blood; CD4 Positive T Lymphocytes; Cells; Centers for Disease Control and Prevention (U.S.); Cercocebus; Cercocebus atys; Computer Retrieval of Information on Scientific Projects Database; Disease Progression; Exhibits; Funding; Grant; HIV Infections; Helper-Inducer T-Lymphocyte; Human; Influenza; Influenza vaccination; Institution; Macaca; Plasma; Primates; Research; Research Personnel; Resources; Role; SIV; Source; T-Cell Depletion; T-Lymphocyte; T-Lymphocyte Subsets; Testing; United States National Institutes of Health; Vaccinated; Viral Load result; Virus Diseases; lymph nodes

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 对于人类 HIV 感染和猕猴猿免疫缺陷病毒 (SIV) 感染，CD4+ T 细胞耗竭与疾病进展速度加快之间的关联已得到充分证实。 在我们的研究之前，观察到 SIV 感染其天然灵长类宿主（即乌白眉猴）会导致 CD4+ T 细胞接近正常水平，尽管血浆病毒载量相似。 在 2000 年和 2006 年从 SIV+ 白眉猴转移血浆后，五只白眉猴的 CD4+ T 细胞水平下降至每微升血液 100 个细胞以下，这在淋巴结中也观察到。 过去 9 年里，这些水平一直保持在 18 至 100 个细胞/ul 血液之间。在 Yerkes 群体中，SIV+白眉猴中存在定义为 AIDS 的 CD4+T 细胞水平的情况并不常见（在筛选的 105 只 SIV+白眉猴中，只有 4 只 CD4 低）。 我们最近测试了这五 (5) 只低 CD4 SIV+ 白眉猴对流感疫苗接种的反应能力。 我们给它们接种了两次疫苗，并将血浆送到疾病预防控制中心进行分析，以量化流感特异性抗体的水平。 通过微量中和测定和血凝抑制，确定所有五只白眉猴都能对流感疫苗产生有效的抗体反应，即使 CD4+ T 细胞水平非常低。 我们现在正在评估这些白眉猴中的各种 T 细胞亚群，以确定哪些亚群可能在这些 SIV+ CD4-低白眉猴中发挥 T 辅助细胞的作用。 迄今为止的努力已确定 CD3+/CD4-/CD8-（双阴性）T 细胞是最有可能的候选者。