Autologous or allogeneic bone marrow transplantation is of major interest to transplant surgeons as a method of inducing adult chimerism for producing specific allograft acceptance without chronic immunosuppression. In allogeneic bone marrow transplantation, one of the major problems is graft-versus-host disease (GVHD), which can be partly prevented by mature T-cell removal prior to transplant. T-cell depletion, however, is associated with an increased incidence of graft failure. The objectives of these detailed studies are to prevent GVHD and circumvent marrow graft rejection or lack of engraftment by pretreatment of the bone marrow inoculum with ultraviolet B (UVB) irradiation and, thus, to induce permanent allograft acceptance in adult animals. Since the applicants have already shown in preliminary studies that UVB prevents GVHD in a fully allogeneic rat bone marrow transplantation model, they now plan to determine the mechanism of UVB prevention of GVHD with particular emphasis on the UVB effect on phenotypic and functional cell alteration of the inoculum. They also plan to perform detailed evaluations of recipients' functional myelopoietic and lymphoid reconstitution. These studies in rodents on induction of adult chimeras without GVHD will serve as the basis of further studies on the use of UVB treated bone marrow in a preclinical cynomologous monkey model of autologous and allogeneic bone marrow transplantation in preparation for clinical bone marrow transplantation and allogeneic organ transplantation.
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