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，激活状态和生存能力。 HIV-1感染靶标可能会以多种方式影响NK细胞。包括HIV-1包膜与激活NK细胞表达的趋化因子受体的相互作用以及与HIV-1诱导的HIV-1疾病中细胞因子表达的调节的关系。在第一个目标中，我们建议通过在体外感染了HIV-1感染的自体CD4+原代T细胞来分析NK，并测试病毒诱导的NK激活状态，生存力和增殖能力的调节。我们将在目标细胞相互作用后通过CD107A暴露来评估NK激活，并通过RNase保护分析表征促炎和凋亡相关的基因表达。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，以检验一般的假设，即在没有附属细胞帮助的情况下，NK细胞在裂解HIV感染的靶标方面受到了损害。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，并可能确定干预的新目标。