| Though it has been clearly demonstrated in rodent systems that purified hematopoietic stem cells (HSC) alone are sufficient to engraft lethally irradiated allogeneic recipients, it has long been suggested that there are populations of cells which will facilitate such HSC engraftment. Populations from thoracic duct, whole bone marrow, lymph node, thymus, peripheral blood, and mobilized peripheral blood have been shown to facilitate. In this study, several subpopulations of WBM were evaluated for facilitative potential by comparative analysis of survival and reconstitution in mice reconstituted with HSC alone and HSC plus additional non HSC bone marrow subpopulations. The CD8α+ population was found to be the most efficient WBM facilitative population, with potential being detected in both the TCR + and TCR− subpopulations. Cells of the CD8 +TCR+ population have the morphology and surface marker patterns of typical T-lymphocytes. Cells of the CD8+TCR − population have a granular morphology and are CD8β −, CD11c+ and predominantly CD3− . Multiple mechanisms have been proposed to explain facilitation. These studies demonstrated that neither lytic function nor alloreactivity was necessary for facilitation, and that the CD8α molecule was either directly important for facilitation or important in the development of the potential to facilitate.; As success with allotransplantation of hematopoietic populations improves, the use of this therapeutic modality will expand into other fields, i.e. solid organ transplantation. The use of transplantation of purifed hematopoietic stem cells in tolerance induction for solid organ transplantation was explored in these studies. It was demonstrated that infusion of purified hematopoietic stem cells alone in lethally irradiated mice is sufficient for tolerance induction, that stem cell transplantation can be performed prior to or simultaneously with the solid organ transplant, and that the use of facilitator cells to enhance hematopoietic engraftment will not compromise tolerance induction.; Finally, BCL-2 expression in the lethally irradiated environment was studied. It was demonstrated that endogenous BCL-2 was expressed at higher levels after irradiation, and that overexpression of BCL-2 in purified HSC improved survival following irradiation. |
