The proposal consists of three objectives. First, Is GH required for maintenance of thymic and bone marrow cellularity? Does GH ablation result in reduced cellularity of thymus and bone marrow? The applicant predicts that in the absence of GH there will be reduction in thymic size involving loss of cortical thymocytes and accumulation of CD4- CD8- T cell progenitors. The reduction in bone marrow cellularity will be accompanied by a reduction in multipotent myeloid progenitors. He predicts that these changes will be reversed by GH administration and that this will establish that GH ablation is a valid model for immunosenescence. Second, does GH act as a survival factor in lymphoid and myeloid progenitors in vivo by preventing apoptosis? The applicant hypothesizes that GH promotes survival by maintaining expression of the protooncogene bcl-2 and that withdrawal of GH will result in induction of apoptosis in thymocytes and myeloid progenitors associated with a decrease in BCL-2 levels. Third, the applicant will use highly purified CD34+ cells and flow cytometry to ask if pluripotent hematopoietic progenitors express receptors for GH and IGF-I. Collectively it is hypothesized that these experiments will establish the concept that GH maintains lymphoid and myeloid tissues in vivo by promoting the survival of lymphoid and myeloid progenitors and thus will provide new and important insights into aging of the immune system.
