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: 10919145
• 负责人: Matthew E Brown
• 金额: $ 38.75万
• 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 2024-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10919145
• 关键词: Alleles; Antigen-Presenting Cells; 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; Mouse Strains; Mus; Myeloid Cells; Natural Immunity; Neonatal; Pathology; Source; Study models; T-Cell Development; T-Lymphocyte; Testing; Thymic Tissue; Thymus Gland; Tissues; Transgenes; Transplantation; Universities; Work; adaptive immunity; comparative; fetal; hematopoietic engraftment; 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.

该项目的重点是从胎儿与新生儿人类组织来源制备的人源化免疫系统（HIS）小鼠的直接比较和免疫学分析。 将优化新生儿HIS模型，以更好地再现全身和组织特异性人类先天性和适应性免疫以及淋巴组织发育。将开发两种新型人源化小鼠宿主品系，并评价其在无辐照的情况下产生稳健的人免疫细胞植入和功能的能力。将通过研究T细胞介导的移植同种异体排斥反应和通过使用Epstein巴尔病毒（EBV）检查感染性疾病病理学来评估所开发的模型。Matthew Brown博士将担任主要研究者;这项工作将与马萨诸塞州大学（Michael Bohm博士）和杰克逊实验室（伦纳德舒尔茨博士）合作完成。这些研究将使用他们拥有的先前冷冻保存的胎仔组织。本研究不会采集新的胎仔组织。