Development of immune function following bone marrow transplantation is usually delayed by the long time required for hematopoietic stem cells to differentiate into mature T lymphocytes. The capacity to generate new T lymphocytes differs between BMT patients, suggesting that there are significant differences in thymic function. The hypothesis tested in this proposal is that differences in T cell regeneration and immune function following BMT are due to individual differences in the capacity for IL-7 production. IL-7 is a stroma derived cytokine which is an important mediator of thymocyte growth and differentiation. The capacity to produce IL-7 may be an inmportant determinant of post-BMT T lymphocyte production and immune competence. The proposed studies will evaluate the role of IL-7 in T lymphocyte regenration, development of antigen-specific T and B cell responses and in the prevention of clinical infection. Patients will be longitudinally evaluated for Il-7 production before BMT, measuring both plasma IL-7 levels and in vitro production from bone marrow stroma cultures. Serial increases in the number of T lymphocytes will be measured by immunophenotyping. Routine immunization at fixed time points after BMT will be used to assess immunocompetence. The relationship between IL-7 levels and thymic regeneration, immune function and clinical outcome will be analyzed.
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