T cell responses and cardiac transplantation in infancy

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Those who receive a cardiac transplant in the early months of life typically are typically subjected to thymectomy and their T cells are depleted with anti-T cell antibodies. These treatments and the ongoing immunosuppression with which the patients are treated profoundly change the T cell compartment. For example, few recent thymic emigrants are found in the blood and the T cell receptor repertoire is notably contracted. Despite these changes, infants with cardiac transplants do not exhibit the manifestations typical of severe immunodeficiency. The well being of these patients presumably occurs because the residual T cells undergo compensatory proliferation and functional changes. Those participating in this project will study patients who underwent cardiac transplantation early in life and patients who received non-transplant cardiac surgery and hence thymectomy to determine how the repertoire and function of the T cell compartment is changed, what implications these changes have for the well being of the patient (such as viral load and autoimmunity), and whether surgical and medical manipulations might be undertaken to prevent or reverse these changes. Controls will include transplant recipients with intact thymus, subjects with thymectomy but no transplant, and normal individuals of the same age. The research will establish patients with cardiac transplantation early in life or non-transplant cardiac surgery as a standard model for compensatory changes in the T cell compartment. The patients studied will be through collaboration with Dr. West (Project 1); analysis of T cell responses, particularly T cell dependent B cell responses and autoimmunity will be through collaboration with Dr. Cascalho (Project 2); and testing of therapeutic regimens will be in collaboration with Dr. Zhong (Project 4).