T cell compartment dynamics following thymectomy

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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.