Dissociation of hemopoietic chimerism and allograft tolerance after allogeneic bone marrow transplantation

Creation of stable hemopoietic chimerism has been considered to be a prereq uisite for allograft tolerance after bone marrow transplantation (BMT). In this study, we demonstrated that allogeneic BMT with bone marrow cells (BMC ) prepared from either knockout mice deficient in both CD4 and CD8 T cells or CD3E-transgenic mice lacking both T cells and NK cells maintained a high degree of chimerism, but failed to induce tolerance to donor-specific wild -type skin grafts. Lymphocytes from mice reconstituted with T cell-deficien t BMC proliferated when they were injected into irradiated donor strain mic e, whereas lymphocytes from mice reconstituted with wild-type BMC were unre sponsive to donor alloantigens. Donor-specific allograft tolerance was rest ored when donor-type T cells were adoptively transferred to recipient mice given T cell-deficient BMC. These results show that donor T cell engraftmen t is required for induction of allograft tolerance, but not for creation of continuous hemopoietic chimerism after allogeneic BMT, and that a high deg ree of chimerism is not necessarily associated with specific allograft tole rance.