DELINEATION OF MULTIPLE SUBPOPULATIONS OF NATURAL KILLER CELLS IN MONKEYS

猴子自然杀伤细胞多个亚群的划分

• 批准号: 7958316
• 负责人: R. PAUL JOHNSON
• 金额: $ 19.97万
• 依托单位: HARVARD MEDICAL SCHOOL
• 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/7958316
• 关键词: Acquired Immunodeficiency Syndrome; Biological Assay; Cells; Color; Computer Retrieval of Information on Scientific Projects Database; Disease model; Flow Cytometry; Funding; Future; Grant; Human; Immune response; Institution; Lymphocyte; Lymphocyte Homing Receptors; Macaca; Macaca mulatta; Minor; Monkeys; Natural Killer Cells; New England; Pathogenesis; Population; Primates; Research; Research Personnel; Resources; Role; Source; United States National Institutes of Health; Work; base; chemokine; improved; response

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. NK cells in rhesus macaques have been variably defined as CD3-negativeCD16-positive or CD3-negativeCD8-positive, although only limited efforts have been made to rigorously validate these definitions. To better understand the role of NK cells in macaque disease models, we undertook a multiparameter analysis of macaque NK cells employing four color flow cytometry and a panel of lineage-specific and non-lineage specific lymphocyte markers. Using this approach, we recently identified two distinct populations of candidate NK cells: a major CD8brightCD16-positive population and a minor CD8brightCD16-negative population. In addition, a CD56-positive subset of cells within the minor rhesus NK population was identified that expressed chemokine and lymph node homing receptors similar to those expressed by the CD56bright NK cell population identified in humans. This work has now been extended using 8 color flow cytometry and has verified the existence of this different populations of NK cells. In addition, we have developed a functional flow cytometric assay for the ability of NK cells to degranulate in response to stimulation with target cells. These improved immunophenotypic definitions of macaque NK cells should facilitate future analysis of innate immune responses in rhesus macaques and the role of NK cells in AIDS pathogenesis in SIV-infected macaques.

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。 恒河猕猴中的NK细胞被多样地定义为CD3-NegativeCD16阳性或CD3-NegativeCD8阳性，尽管仅采取了有限的努力来严格验证这些定义。 为了更好地了解NK细胞在猕猴疾病模型中的作用，我们对使用四个颜色流式细胞仪和一组谱系特异性和非Lineage特异性淋巴细胞标记的猕猴NK细胞进行了多参数分析。 使用这种方法，我们最近确定了两个不同的候选NK细胞种群：主要的CD8BrightCD16阳性人群和一个次要的CD8BrightCD16阴性人群。 此外，鉴定出少数恒河类群中的CD56阳性细胞的子集，该细胞被鉴定出表达的趋化因子和淋巴结的归因受体，类似于人类鉴定的CD56Bright NK细胞群体表达的趋化因子和淋巴结。 现在使用8个彩色细胞仪扩展了这项工作，并验证了这种不同的NK细胞种群的存在。 此外，我们开发了一种功能流式细胞术测定，用于NK细胞响应靶细胞刺激而脱粒的能力。 这些改善的猕猴NK细胞的免疫表型定义应促进对恒河猕猴先天免疫反应的未来分析，以及NK细胞在SIV感染猕猴中的AIDS发病机理中的作用。