The influence of graft-versus-host reactivity, lymphocyte depletion, and cell dose on allogeneic bone marrow engraftment.
Graft rejection has hampered the use of T cell depletion (TCD) in allogeneic bone marrow transplantation. A model of host-versus-graft (HVGR) and graft-versus-host reaction (GVHR) as two inversely related processes has been proposed. We investigated graft rejection rates in graft-versus-host-reactive and graft-versus-host-nonreactive situations in a rat and a mouse model. Model 1: LEW rats were pretreated with a fixed myeloablative dose of busulfan and increasing doses of the immunosuppressive cyclophosphamide. The animals received different doses of semiallogeneic GvH-nonreactive BM cells. Graft rejection rates were dependent on the bone marrow cell number transplanted and on the pretransplant immunosuppression. Graft rejection rates following transplantation of GvH-reactive CAP marrow and genetically GvH-nonreactive (CAP x LEW)F1 marrow were the same. In conclusion, there was no advantage with respect to engraftment for the GvH-reactive marrow. Model 2: In irradiated Balb/c mice, graft rejection rates following T cell-depleted and unmanipulated transplantation of GvH-reactive or GvH-nonreactive bone marrow grafts were identical. All experiments were done with graded numbers of BM cells and revealed a strong impact of the BM cell dose on engraftment. In our experiments the cell loss during the ex-vivo manipulation was approximately 50% and, in contrast to the clinical situation, we readjusted to the intended number after TCD. Our experiments demonstrate that neither GvHR nor T cells but the BM cell dose has a strong impact on engraftment of allogeneic bone marrow.
Glass
B
B
Department of Internal Medicine II, University of Kiel, Germany.
Uharek
L
L
Gaska
T
T
Gassmann
W
W
Löffler
H
H
Müller-Ruchholtz
W
W
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology*; D002066:Busulfan / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection; D006087:Graft vs Host Reaction / Q000276:immunology / Q000502:physiology*; D006789:Host vs Graft Reaction / Q000502:physiology; D016867:Immunocompromised Host; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D014184:Transplantation, Homologous
D003520:Cyclophosphamide; D002066:Busulfan