Direct/Indirect NK Activation by HIV-1 Infected Cells

HIV-1 感染细胞直接/间接 NK 激活

• 批准号: 7060620
• 负责人: Costin Tomescu
• 金额: $ 4.6万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7060620
• 关键词: HIV infections; RNase protection assay; cell cell interaction; cell mediated cytotoxicity; cell proliferation; chemokine receptor; chemotaxis; clinical research; dendritic cells; gene expression; helper T lymphocyte; human subject; interferon gamma; interleukin 12; leukocyte activation /transformation; leukocyte count; lymphocyte; monocyte; natural killer cells; postdoctoral investigator; tissue /cell culture

DESCRIPTION (provided by applicant): The overall goal of this proposal is to contribute to the understanding of how HIV-1 infected target cells influence NK cell phenotype, activation state, and viability. HIV-1 infected targets may influence NK cells in several ways; including HIV-1 envelope interactions with chemokine receptors expressed on activated NK cells and their relation to HIV-1 induced modulation of cytokine expression during HIV-1 disease. In the first aim, we propose to analyze NKs by incubating PBMCs with autologous CD4+ primary T cells infected with HIV-1 in vitro and testing for virus-induced modulation of NK activation state, viability, and proliferative capacity. We will evaluate NK activation by CD107a exposure upon target cell interaction and characterize proinflammatory and apoptosis related gene expression by RNase protection assays. In the second aim, we will investigate the accessory role of dendritic cells in NK recognition and killing of HIV-1 infected target cells, in order to test the general hypothesis that NK cells are impaired in their ability to lyse HIV-infected targets in the absence of accessory cell help. Overall, this research will improve our understanding of mechanisms of control of HIV and potentially identify new targets for intervention.

描述（由申请人提供）：该提案的总体目标是有助于理解 HIV-1 感染的靶细胞如何影响 NK 细胞表型、激活状态和活力。 HIV-1 感染目标可能以多种方式影响 NK 细胞；包括 HIV-1 包膜与活化 NK 细胞上表达的趋化因子受体的相互作用，以及它们与 HIV-1 疾病期间 HIV-1 诱导的细胞因子表达调节的关系。在第一个目标中，我们建议通过在体外将 PBMC 与感染 HIV-1 的自体 CD4+ 原代 T 细胞一起孵育来分析 NK，并测试病毒诱导的 NK 激活状态、活力和增殖能力的调节。我们将评估靶细胞相互作用时 CD107a 暴露对 NK 的激活作用，并通过 RNase 保护测定来表征促炎和凋亡相关基因表达。在第二个目标中，我们将研究树突状细胞在 NK 识别和杀死 HIV-1 感染靶细胞中的辅助作用，以检验 NK 细胞在没有辅助细胞帮助的情况下裂解 HIV 感染靶细胞的能力受损的一般假设。总体而言，这项研究将提高我们对艾滋病毒控制机制的理解，并有可能确定新的干预目标。