This project describes studies of hematopoietic reconstitution after marrow transplantation. The frequency and clinical significance of mixed hemopoietic and lymphoid chimerism after marrow transplantation will be evaluated. Patients with donors of the opposite sex will be studied for hematopoietic chimerism of various cell populations including B-cells, T-cells, committed hematopoietic progenitors cultured directly and from long-term marrow cultures, and marrow microenvironmental cells that form the adherent cell layers in long-term marrow cultures. The techniques used will involve clonal expansion of each of these cell populations. SV-40 virus will be used to transform and develop clones of microenvironmental cells and EB virus will be used to transform B-cells. The second part of this project will be an examination of pre- colony forming hematopoietic progenitors in manipulated marrow samples from normal donors and from recipients of allogeneic marrow. These studies rely on the recent observations that by using monoclonal antibodies directed against myeloid differentiation antigens, it is possible to define and measure a progenitor cell that does not form colonies but has the capability of producing multipotent and unipotent colony-forming progenitors in long-term marrow culture. These assay systems will be employed to examine the proliferative defect present in vitro after marrow transplantation and to measure the earliest detectable hematopoietic progenitors in marrows subjected to manipulations such as T-cell depletion which appear to increase the risk of graft rejection. Since it is possible to measure the proliferative potential of these early progenitors in the absence of potentially growth-modulating cell populations, it should be possible to determine whether the in vitro proliferative defect after marrow grafting is due to a decrease in number and/or proliferative capacity of early progenitors or due to growth modulation in vitro by other cell populations.
Showing the most recent 10 out of 1845 publications
