It is the goal of the Project IV to test the hypothesis that the T cells (including CD4+ and CD8+ subsets) in the bone marrow are qualitatively different than those in the peripheral blood of normal mice, and that after treatment with G-CSF these marrow T cells are mobilized into the blood. Furthermore, we theorize that these marrow T cells, on a cell per cell basis, have a markedly reduced capacity to induce lethal graft versus host disease (GVHD) after allogeneic marrow transplantation as compared to blood T cells, but yet retain graft versus leukemia (GVL) effect and/or graft facilitation activities. In order to test the hypothesis, we will compare the surface markers, migration pathways, cytokine secretion patterns and capacity to induce lethal GVHD, mediate GVL and graft facilitation using highly purified T cell subsets from the bone marrow and blood of normal mice, and from mice treated with G-CSF. Blood T cell subsets of normal humans will be compared before and after treatment with G-CSF also. Purified donor T cell subsets will be obtained by flow cytometry, and injected along with T cell depleted donor bone marrow cells into MHC matched or mismatched recipient mice given lethal whole body irradiation. GVL activity will be measured using the BCL1 B cell leukemia, and graft facilitation will be measured using purified stem cells. The results of the study should help design clinical protocols of allogeneic marrow or mobilized blood cell transplantation to reduce GVHD and tumor relapse.
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