Transplantation Tolerance through Hematopoietic Chimerism

Stunning advances in human transplantation have been tempered by the immunologic consequences of histoincompatibility between donor and recipient — namely, allograft rejection after solid-organ transplantation and graft-versus-host disease (GVHD) after hematopoietic stem-cell (bone marrow) transplantation (HSCT). The separation of GVHD from the graft-versus-tumor effect and the induction of functional immune tolerance, defined by the absence of a destructive immune response in the absence of systemic immunosuppression, have been considered the “Holy Grail” of HSCT and solid-organ transplantation, respectively. Freedom from immunosuppression after organ transplantation has a tremendous potential upside, since lifelong immunosuppressive therapy is sometimes complicated by debilitating or life-threatening . . .