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 allo geneic bone marrow transplantation. A model of host-versus-graft (HVGR ) and graft-versus-host reaction (GVHR) as two inversely related proce sses 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 fixe d myeloablative dose of busulfan and increasing doses of the immunosup pressive cyclophosphamide. The animals received different doses of sem iallogeneic GvH-nonreactive BM cells. Graft rejection rates were depen dent on the bone marrow cell number transplanted and on the pretranspl ant 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 r espect to engraftment for the GvH-reactive marrow. Model 2: In irradia ted Balb/c mice, graft rejection rates following T cell-depleted and u nmanipulated transplantation of GvH-reactive or GvH-nonreactive bone m arrow grafts were identical. All experiments were done with graded num bers of BM cells and revealed a strong impact of the BM cell dose on e ngraftment. In our experiments the cell loss during the ex-vivo manipu lation was aproximately 50% and, in contrast to the clinical situation , we readjusted to the intended number after TCD. Our experiments demo nstrate that neither GvHR nor T cells but the BM cell dose has a stron g impact on engraftment of allogeneic bone marrow.