T cell compartment dynamics following thymectomy

描述(申请人提供)：我的长期目标是开发重建豁免权的方法。免疫重建将使那些因疾病或衰老而患有免疫缺陷的人受益，并可能被用于产生针对感染和癌症的特定疗法。鉴于我在数学、工程学和人工器官设计方面的背景，以及我目前在移植生物学方面的博士后研究，我非常有能力推进这一领域的研究。我在这里建议，朝着这一目标发展职业生涯的第一步。 我的近期目标将是了解人类婴儿的T细胞室如何在婴儿心脏手术时进行胸腺切除和T细胞耗尽时发生变化。这些操作应该会通过移除新的T细胞的来源，并耗尽一些现有的T细胞，从而严重扭曲免疫系统的生理。然而，这些患者维持着合理的健康。我假设，那些在婴儿期接受心脏移植或其他类型心脏手术的人的相对健康是由于残留T细胞的扩张以及引发免疫反应所必需的功能要求的相关变化。验证这一假设将使我能够探索免疫重建的自然手段，并评估我设计的衡量免疫适应性的新技术和方法。 这项研究计划将通过正规的免疫学培训和杰弗里·普拉特博士的指导来补充。此外，还将组建一个顾问委员会，成员包括Marilia Cascalho博士和Mark Litzow博士。该理事会将每半年举行一次会议，以评估研究计划和职业计划的进展情况。该计划将提供必要的职业发展，以启动在生物医学的独立研究生涯。

DESCRIPTION (provided by applicant): My long-term goal is to develop the means to reconstitute immunity. Immune reconstitution would benefit those who suffer immunodeficiency as a result of disease or aging and might be used to generate specific therapies for infection and cancer. Given my background in mathematics, engineering and artificial organ design and my current postdoctoral fellowship in transplantation biology, I am uniquely poised to advance this area of research. I propose here a first step in developing a career directed toward that goal. My proximal goal will be to learn how the T cell compartment of human infants changes in response to thymectomy and T cell depletion carried out at the time of cardiac surgery in infancy. These manipulations should severely distort the physiology of the immune system by removing the source of new T cells, and depleting some of those T cells already present. However, these patients uphold reasonable health. I hypothesize that the relative well being of those who had cardiac transplants or other types of cardiac surgery in infancy results from the expansion of residual T cells and an associated change in functional requirements necessary to elicit an immune response. Testing this hypothesis will allow me to explore natural means of immune reconstitution and evaluate new technologies and methods I have devised to measure immune fitness. This research plan will be complemented by formal training in immunology and by mentorship with Dr. Jeffrey Platt. In addition, an advisory council will be assembled to include Drs. Marilia Cascalho and Mark Litzow. This council will meet on a semiannual basis to evaluate progress in the research plan and the career plan. This program will provide the career development necessary to launch an independent research career in biomedicine.