Functional analysis of human NKT cells and myeloid DCs within murine SCID hosts

小鼠 SCID 宿主体内人类 NKT 细胞和髓样 DC 的功能分析

• 批准号: 7356104
• 负责人: Jenny E. Gumperz
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-22 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7356104
• 关键词: Affect; Agonist; Antigens; Biological Models; Cell physiology; Cells; Clinical; Clone Cells; Complex; Data; Dendritic Cells; Exposure to; Future; Glycolipids; Goals; Grant; Human; Immune; Immune response; Immunology; In Vitro; Injection of therapeutic agent; Intravenous; Leukocytes; Life; Mus; Myelogenous; Myeloid Cells; Peripheral; Phenotype; Population; Production; Property; Recruitment Activity; Research; Route; SCID Mice; Stimulus; Stream; System; T-Cell Activation; T-Cell Proliferation; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Thioglycolates; Time; Tissue Survival; Tissues; Translating; Tube; abstracting; antimicrobial; base; cytokine; immune function; in vivo; intraperitoneal; monocyte; peripheral blood; response; trafficking; tumor

DESCRIPTION (provided by applicant): NKT cells comprise a small T cell subset that appears to have far-reaching and remarkably varied effects on immune function. The mechanisms by which NKT cells affect down-stream immune responses remain poorly understood. In our preliminary studies we have observed that human NKT cells direct fresh peripheral blood monocytes to differentiate into dendritic cells (DCs) in vitro. The resulting DCs have a unique regulatory phenotype, and appear to silence MHC-restricted T cell activation. Hence, we hypothesize that promoting the differentiation of regulatory DCs is one mechanism by which NKT cells can broadly affect immune responses. However, it remains unclear whether NKT cells can perform this function in vivo. Here we propose i) to test the ability of human NKT cells to direct human monocyte differentiation into DCs after transfer into SCID-mouse hosts, and ii) to investigate the functional properties of NKT cell-induced human DCs within the SCID mice. Abstract Narrative: This grant proposes to use an in vivo SCID mouse system to investigate the functions of human NKT cells in promoting monocytes to differentiate into DCs, and to test the functional properties of the resulting DCs.

描述（由申请人提供）：NKT细胞包含一个小的T细胞子集，该子集似乎对免疫功能具有深远的影响且巨大的影响。 NKT细胞影响下游免疫反应的机制仍然很少理解。在我们的初步研究中，我们观察到人NKT细胞在体外指导新鲜的外周血单核细胞分化为树突状细胞（DC）。所得的DC具有独特的调节表型，并且似乎使MHC限制的T细胞激活保持沉默。因此，我们假设促进调节DC的分化是NKT细胞可以广泛影响免疫反应的一种机制。但是，尚不清楚NKT细胞是否可以在体内执行此功能。在这里，我们建议i）测试人NKT细胞在转移到SCID鼠宿主后将人单核细胞分化为DC的能力，ii）研究SCID小鼠内NKT细胞诱导的人DC的功能特性。 摘要叙述：该赠款建议使用体内SCID小鼠系统研究人NKT细胞在促进单核细胞中分化为DC中的功能，并测试所得DC的功能特性。