Complement C1q Function in Allogeneic Transplantation

描述（由申请人提供）：本修订提案描述了一个为期5年的培训计划，用于发展移植生物学的学术生涯。首席研究员已完成了移植生物学研究奖学金。该计划将为研究人员提供资源，以扩大他的研究技能，发展成为移植免疫学的独立研究者。 大卫湖帕金斯，医学博士，博士将指导首席研究员的科学发展珀金斯博士是一位有着20年研究经验的资深研究员，他的研究员们已经开始了学术生涯。该计划将包括格雷戈里L.斯塔尔博士，补体专业知识。由受人尊敬的医学科学家组成的咨询委员会将通过提供科学和职业建议为研究者提供建议。 假设是：移植物C1q通过树突状细胞为介导排斥反应的受体T细胞适应性同种免疫反应提供关键的激活触发。 研究将集中在补体成分C1q在移植排斥反应中的作用。Perkins博士实验室的主要研究者最近的工作表明，Clq缺陷移植物的移植存活时间延长。具体目标包括：1）供体移植物中C1q缺陷是否会降低受体T细胞反应？通过应用体内细胞运输通过转基因GFP小鼠移植C1q的情况下，心脏移植的小鼠模型，我们将确定的效应功能，激活，细胞因子的产生和调节的CD4和CDS T细胞浸润C1q缺陷的同种异体移植物。2)C1q是否调节移植后树突状细胞的活化和成熟？使用转基因GFP小鼠在小鼠心脏移植中存在或不存在移植物C1q的体内细胞运输模型，我们将确定C1q是否是树突状细胞活化和成熟的关键组成部分。这项建议的地点，布里格姆妇女医院，提供了一个很好的设置和建立跟踪记录的医生，科学家的培训。长期目标是培养一名在移植免疫学领域取得成功的医生科学家。

DESCRIPTION (provided by applicant): This revised proposal describes a 5-year training program for the development of an academic career in transplantation biology. The principal investigator has completed a research fellowship in transplantation biology. This program will afford the investigator resources to expand his research skills to develop into an independent investigator in transplantation immunology. David L. Perkins, M.D., Ph.D. will mentor the principal investigator's scientific development. Dr. Perkins is an established investigator with 20 years of research experience whose fellows have gone on to academic careers. The program will include the assistance of Gregory L. Stahl, PhD with expertise in Complement. An advisory committee of respected medical scientist will advise the investigator by providing scientific and career advice. The hypothesis is: Graft C1q provides crucial activating triggers via dendritic cells for the recipient T cell adaptive alloimmune response that mediates rejection. Research will focus on the role of Complement component C1q in transplantation graft rejection. Recent work by the Principal Investigator in Dr. Perkins's laboratory shows prolonged graft survival in Clq deficient transplants. The specific aims include: 1) Does C1q deficiency in the donor graft decrease recipient T cell responses? By application of in vivo cell trafficking via transgenic GFP mice to a murine model of heart transplantation in the absence of graft C1q, we will determine the effector function, activation, cytokine production and regulation of CD4 and CDS T cells infiltrating C1q deficient allografts. 2) Does C1q modulate dendritic cell activation and maturation following transplantation? Using a model of in vivo cell trafficking via transgenic GFP mice in murine heart transplantation in the presence or absence of graft C1q, we will determine if C1q is crucial component of the activation and maturation of dendritic cells. The location for this proposal, the Brigham and Women's hospital; provides an excellent setting and an established track record for the training of physician-scientists. The long-term goal is to train a physician-scientist that will succeed in the field of transplantation immunology.