Nonmyeloablative conditioning to induce bilateral tolerance after allogeneic bone marrow transplantation in mice

We recently described a new nonmyeloablative method to induce stable and sp ecific transplantation tolerance to allogeneic tissues in adult mice, It in cluded total lymphoid irradiation (TLI) of recipients with six fractions of 200 cGy each, inoculation with donor bone marrow (BM) cells and cyclophosp hamide (Cy) for selective elimination or inactivation of residual donor-rea ctive cells of the host, and infusion with T-cell depleted donor BM cells a fter Cy, Here, we investigated the possibility to induce stable bilateral g raft-vs-host and host-vs-graft transplantation tolerance using non-T-cell d epleted allogeneic BM, Our results show that the dose of BR I required for the induction of transplantation tolerance was inversely correlated with th e intensity of the conditioning, Transfer of a low dose (3 X 10(6)) of tota l donor Bnl cells to recipients pl preconditioned with a less intensive reg imen (two or three TLI fractions instead of sis) diminished graft-vs-host d isease (GVHD)-related mortality of recipients to 40% and converted 89% of t he survivors into GVHD-free mixed hematopoietic chimeras that maintained do nor skin allografts >180 days, A tenfold increase in the number of donor BM cells (3 X 10(7) instead of 3 X 10(6)) reduced the rate of GVHD-related mo rtality of recipients to 20% and resulted in bilateral transplantation tole rance in 100% of nonirradiated survivors. (C) 1999 International Society fo r Experimental Hematology. Published by Elsevier Science Inc.