The elimination from marrow of cells expressing T cell surface markers is of interest both in allogeneic and autologous marrow transplantation -- as a means of preventing graft versus host disease in allogeneic marrow transplantation and as a means of eliminating or purging malignant cells expressing T cell surface markers from marrow in treating T cell neoplasms by autologous marrow transplantation. Approaches were developed for depleting normal and malignant T cell marrow populations by using elutriation and deriving monoclonal antibodies specific for cell surface molecules unique to T cells. These approaches were used to develop clinical protocols to assess the feasibility of utilizing allogenic HLA-mismatched, T cell depleted allogeneic marrow and autologous marrow purged of malignant T cells in the treatment of aggressive hematolymphopoietic malignancies. Preclinical studies in rhesus monkeys demonstrated that functional T cell populations are generated in animals receiving T cell depleted autologous marrow. The time course of CD4+ T cell reconstitution and development of in vivo T cell immunocompetence correlated with the number of T cells infused in the marrow, and did not correlate with marrow cell dose or hematopoietic reconstitution, raising the possibility that residual T cells in the infused T cell depleted marrow played a central role in the generation of subsequent T cell populations. The mechanisms by which infused, mature T cells generate reconstituting peripheral T cell populations is under investigation in murine models. The functional capacities of these regenerated T cell populations is also of interest. The human T helper cell response to xenogenic MHC encoded antigens expressed by stimulating murine cell populations has been studied and found to be of special use in the assessment of human T helper cell function in that this

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Division of Cancer Biology and Diagnosis
United States
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