The goal of this application is to test the hypothesis that the T cells in bone marrow are qualitatively different than those in peripheral blood of normal mice and that after treatment with G-CSF, marrow T cells are mobilized into the blood. Preliminary data have suggested that marrow T cells have a markedly reduced capacity to induce lethal graft-versus-host disease after allogeneic marrow transplantation as compared to blood T cells but retain graft-versus-leukemia activity and an ability to facilitate engraftment. In order to test this hypothesis, the applicant will compare the surface markers, migration pathways, cytokine secretion patterns and capacity to induce lethal graft-versus-host disease, mediate graft-versus-leukemia effects and facilitate engraftment by using highly purified T cell subsets from the bone marrow and blood of normal mice and from mice treated with G-CSF. Purified donor T cell subsets will be obtained by flow cytometry and injected together with T cell-depleted marrow in lethally irradiated MHC matched or mismatched recipients. Graft-versus-leukemia activity will be measured with the use of the BCL1 B cell leukemia, and graft facilitation will be measured using purified stem cells. Results of this study should help the design of clinical protocols of allogeneic marrow or mobilized blood cell transplantation in attempts to reduce the risks of graft-versus-host disease and recurrent malignancy.
Showing the most recent 10 out of 23 publications
