Multiplexed single cell cytokine secretion assay

多重单细胞细胞因子分泌测定

基本信息

批准号：
7286299
负责人：
LAWRENCE Michael KAUVAR
金额：
$ 47.39万
依托单位：
EXPERIMED BIOSCENCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-06-15 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7286299
关键词：
Abnormal Cell Algorithms Amino Acid Sequence Antibodies Anticoagulants Antigens Archives Arthritis Asthma Atopic Dermatitis Attention Autoimmune Process Basic Science Biological Assay Biopsy Cell Count Cells Cellular Immunology Chronic Clinical Clinical Research Collaborations Communities Compatible Computer software Condition Cutaneous Data Data Analyses Data Set Databases Development Diagnostic Diagnostic Procedure Disease Documentation Eczema Engineering Freezing Goals Grant Health Heterogeneity Hour Human Immune Immune System Diseases Immune system Immunologist Immunology Individual Infectious Agent Institutes Language Lasers Lead Learning Letters Ligands Link Lung Marketing Measures Mediating Medicine Memory Methods Microscope Normal Cell Normal tissue morphology Numbers Output Pain Patient Monitoring Peptides Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Phase Phenotype Plastics Population Procedures Process Progressive Disease Proteins Psoriasis Qualifying Range Reading Reagent Reporting Reproducibility Research Research Personnel Resolution Role Sampling Secure Seeds Signal Transduction Site Skin Skin Tissue Specimen Staging Standards of Weights and Measures Structure Surface System T cell regulation T-Cell Lymphoma T-Lymphocyte Technology Testing Therapeutic Therapeutic Agents Time Tissues Treatment Protocols Variant Vendor Work base cell type cytokine design immunopathology improved instrument interest lens manufacturing process nanoscale programs prototype quality assurance response task analysis tool

项目摘要

DESCRIPTION (provided by applicant): Immune cells use signals to coordinate their attack on an infectious agent or to downgrade their attack after danger has past. The signals that they use are proteins called cytokines, of which there are about 25. During immunological disorders, cytokines can either signal or control a self-directed attack on the body, and therefore much attention has been paid to cytokines during autoimmune conditions. Yet there are few ways to query individual cells for cytokine expression and until now there have been no ways to do so on the small samples of immune cells isolated from skin and other inflamed tissues. Trellis' approach to measuring single cell cytokine expression is to capture the cytokines produced by single cells while they lie on a flat plastic surface. These cell "footprints" can then be probed by multihued nanoscale beads, each bead type linked to a different anti-cytokine antibody. This method has already revealed that the language of immune cells is not as simple as it is sometimes portrayed. The high level of diversity of immune cells in normal samples may be much diminished in disease or cell types that are rare in normal tissue may become significantly amplified. This is one question that can be explored with Trellis' CellSpot-CK technology. Other questions relate to staging disease based on direct exploration of the cellular profiles that underlie disease manifestation. Such information should be very useful in selecting treatment regimens for these chronic, progressive diseases as well as for monitoring patient responses. Before introducing CellSpot-CK to cellular immunologists throughout the world, Trellis will need to make the instrument used to read CellSpots more robust, easier to use, and faster. This is one Specific Aim in this Phase II proposal. The other Specific Aims relate to characterizing the cytokine language of immune cells in both health and disease. The successful development of CellSpot-CK will make available to researchers a new tool for understanding the role of the immune system in many chronic conditions like eczema, psoriasis, arthritis, and asthma. It will also provide a tool to learn how immune cells respond to drugs under development as cures for these diseases. Longer term, it may provide an important clinical "theranostic" assay (therapy selection based on a diagnostic procedure).

描述（由申请人提供）：免疫细胞使用信号来协调它们对传染源的攻击或在危险过去后降低它们的攻击。它们使用的信号是称为细胞因子的蛋白质，其中约有 25 种。在免疫紊乱期间，细胞因子可以发出信号或控制对身体的自我定向攻击，因此在自身免疫性疾病期间细胞因子受到了很多关注。然而，几乎没有方法可以查询单个细胞的细胞因子表达，而且到目前为止，还没有办法对从皮肤和其他发炎组织中分离出的小量免疫细胞样本进行查询。 Trellis 测量单细胞细胞因子表达的方法是捕获位于平坦塑料表面上的单细胞产生的细胞因子。然后可以通过多色纳米级珠子来探测这些细胞“足迹”，每种珠子类型都连接到不同的抗细胞因子抗体。这种方法已经揭示了免疫细胞的语言并不像有时描绘的那么简单。正常样本中免疫细胞的高水平多样性在疾病中可能会大大减少，或者正常组织中罕见的细胞类型可能会显着增强。这一问题可以通过 Trellis 的 CellSpot-CK 技术来探索。其他问题涉及基于对疾病表现背后的细胞特征的直接探索来对疾病进行分期。这些信息对于选择这些慢性、进行性疾病的治疗方案以及监测患者的反应非常有用。在向世界各地的细胞免疫学家介绍 CellSpot-CK 之前，Trellis 需要使用于读取 CellSpots 的仪器更强大、更易于使用且更快。这是第二阶段提案的一个具体目标。其他具体目标涉及表征健康和疾病中免疫细胞的细胞因子语言。 CellSpot-CK 的成功开发将为研究人员提供一种新工具，用于了解免疫系统在湿疹、牛皮癣、关节炎和哮喘等许多慢性疾病中的作用。它还将提供一种工具来了解免疫细胞如何对正在开发的治疗这些疾病的药物做出反应。从长远来看，它可能提供重要的临床“治疗诊断”测定（基于诊断程序的治疗选择）。