Mixed Bone Marrow Chimeras as an Approach to Transplantation Tolerance
Transplantation tolerance across a complete MHC barrier can be achieved in mice using lethal irradiation followed by reconstitution with a mixture of T-cell-depleted (TCD) syngeneic and allogeneic bone marrow cells.1,2 Such animals repopulate as stable mixed lymphohematopoietic chimeras, and enjoy improved survival compared with recipients of allogeneic TCD marrow alone,3 probably due, in part, to the improved immunocompetence they demonstrate.3 In addition, such animals are free from any clinical sign of graft-versus-host disease (GVHD), and this is also the case even if T-cells are not removed from the allogeneic marrow.4 Experiments in which allogeneic spleen cells were added to the donor inoculum to intentionally produce GVHD indicated that the syngeneic TCD component of the bone marrow inoculum improved the survival of such animals, presumably due to protection from GVHD.4 The data presented in this paper address the possible mechanism of this protective effect. We show that the syngeneic marrow inoculum provides a source of precursor cells which, in recipient spleens, develop the ability to suppress the generation of cytolytic activity by mature T-lymphocytes. We also demonstrate an enhanced protection from GVHD when the syngeneic TCD inoculum is allowed to develop its suppressive activity spontaneously in the recipient before the allogeneic inoculum is given. Such protection could have potential clinical applications.
KeywordsSuppressor Cell Mixed Lymphocyte Reaction Bone Marrow Transplant Recipient Transplantation Tolerance Total Lymphoid Irradiation
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