Characterizing Emerging Humanized Immune Mouse Models for the study of transplant rejection and infectious disease pathology (Epstein Barr Virus)

表征新兴人源化免疫小鼠模型，用于研究移植排斥和传染病病理学（EB 病毒）

• 批准号: 10493887
• 负责人: Matthew E Brown
• 金额: $ 207.66万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-02 至 2024-02-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10493887
• 关键词: Alleles; Biological Models; Cells; Collaborations; Communicable Diseases; Cryopreservation; Development; Engraftment; Evaluation; FLT3 ligand; Fetal Tissues; Graft Rejection; Human; Human Herpesvirus 4; Immune; Immune system; Immunologics; Laboratories; Lymphoid Tissue; Lymphopoiesis; Massachusetts; Measures; Mediating; Modeling; Modification; Mus; Natural Immunity; Neonatal; Pathology; Source; Study models; T-Lymphocyte; Testing; Thymic Tissue; Thymus Gland; Tissues; Transgenes; Transplantation; Universities; Work; adaptive immunity; comparative; fetal; human tissue; humanized mouse; improved; induced pluripotent stem cell; irradiation; mouse model; neonatal human; novel; response

This project focuses on direct comparisons and immunological analyses of humanized immune system (HIS) mice made from fetal vs neonatal human tissue sources. The neonatal HIS model will be optimized to better recapitulate systemic and tissue-specific human innate and adaptive immunity and lymphoid tissue development. Two novel humanized mouse host strains will be developed and evaluated for their ability to generate robust human immune cell engraftment and function without irradiation. The models developed will be assessed by studying T cell-mediated transplant allorejection responses and by examining infectious disease pathology using Epstein Barr Virus (EBV). Dr. Matthew Brown will serve as the PI; the work will be done in collaboration with the University of Massachusetts (Dr. Michael Brehm) and Jackson Laboratory (Dr. Leonard Shultz). Previously cryopreserved fetal tissue in their possession will be used for these studies. No new fetal tissue will be procured for this study.

本项目的重点是直接比较和免疫分析人源化免疫系统（HIS）小鼠从胎儿和新生儿的人体组织来源。新生儿HIS模型将被优化，以更好地概括系统性和组织特异性的人类先天和适应性免疫以及淋巴组织的发育。将开发两种新的人源化小鼠宿主菌株，并评估它们在没有辐照的情况下产生强大的人类免疫细胞植入和功能的能力。开发的模型将通过研究T细胞介导的移植异体排斥反应和使用爱泼斯坦巴尔病毒（EBV）检查传染病病理学来评估。马修·布朗博士将担任PI；这项工作将与马萨诸塞大学（Michael Brehm博士）和杰克逊实验室（Leonard Shultz博士）合作完成。他们拥有的先前冷冻保存的胎儿组织将用于这些研究。本研究不需要新的胎儿组织。