HOST SPECIFIC RESPONSES IN SIV-INDUCED HEMATOSUPPRESSION

SIV 引起的血细胞抑制的宿主特异性反应

• 批准号: 7958249
• 负责人: Guido Silvestri
• 金额: $ 6.8万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958249
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Benign; Bone Marrow; CD4 Positive T Lymphocytes; Cell Count; Cells; Cercocebus; Cercocebus atys; Computer Retrieval of Information on Scientific Projects Database; Defect; Failure; Funding; Grant; Homeostasis; Human; Immune system; Individual; Institution; Macaca mulatta; Mature T-Lymphocyte; Memory; Nature; Primates; Research; Research Personnel; Resources; Role; SIV; Series; Source; T-Cell Proliferation; T-Lymphocyte; United States National Institutes of Health; Virus Diseases; base; regenerative; research study

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. This study focuses on the identification of the defects in the hematopietic and immunological function of the bone marrow during pathogenic and non-pathogenic Simian Immunodeficiency Virus (SIV) infections of rhesus macaques and sooty mangabeys, respectively. These studies allowed us to determine how these defects are involved in causing the overall collapse of the immune system function that is associated with progression to AIDS in HIV-infected individuals. To this end, we are conducting a series of experimental studies in rhesus macaques and sooty mangabeys that have shown that: (i) high levels of mature T-cell proliferation, involving both naive and memory cells, are present in bone marrow-derived cells from uninfected animals; (ii) in SIV-infected SMs, but not RMs, the level of proliferation of bone marrow-based CD4+ T cells is higher than that of circulating CD4+ T cells; and (iii) limited bone marrow-based CD4+ T-cell proliferation in SIV-infected SMs with low CD4+ T-cell counts (suggesting a regenerative failure in these animals). Collectively, these results confirm that the bone marrow is involved in maintaining T-cell homeostasis in primates and suggest a role for bone marrow-based CD4+ T-cell proliferation in determining the benign nature of natural SIV infection of mangabeys. We are hopeful this study will provide information useful to the treatment of bone marrow deficit of HIV-infected humans.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这项研究的重点是鉴定在病原和非致病性邻国免疫缺陷病毒（SIV）感染恒河猴和烟熏芒果的骨髓中造血和免疫学功能中的缺陷。这些研究使我们能够确定这些缺陷如何引起与艾滋病毒感染者辅助相关的免疫系统功能的总体崩溃。为此，我们正在对恒河猕猴和烟熏芒果的一系列实验研究，这些研究表明：（i）来自未感染动物的骨髓衍生的细胞中存在涉及天真和记忆细胞的高水平成熟的T细胞增殖； （ii）在SIV感染的SMS中，而不是RMS中，基于骨髓的CD4+ T细胞的增殖水平高于循环CD4+ T细胞的增殖； （iii）在SIV感染的SMS中，基于骨髓的CD4+ T细胞增殖限制了CD4+ T细胞计数（表明这些动物的再生衰竭）。总的来说，这些结果证实了骨髓参与灵长类动物中的T细胞稳态，并提出了基于骨髓的CD4+ T细胞增殖在确定芒果天然SIV感染的良性性质中的作用。我们希望这项研究将为治疗受HIV感染的人的骨髓不足提供有用的信息。