MIXED HEMATOPOIETIC CHIMERISM AND TRANSPLANTATION TOLERANCE

Durable transplantation tolerance can be reliably achieved by inducing engraftment of hematopoietic cells in recipients initially depleted o f T-lymphocytes. Engraftment of donor pluripotent hematopoietic stem c ells (PPHSC) produces mixed hematopoietic chimeras in which both host and donor cells coexist and are tolerant of each other. The major mech anism of tolerance in these chimeras is central, intrathymic clonal de letion, which is induced and maintained by immigration of both host an d donor marrow-derived cells to the host thymus, ensuring the ongoing central deletion of donor-and host-reactive cells. In this article, ap proaches developed in our laboratory to induce stable mixed hematopoie tic chimerism and specific central deletional allogeneic and xenogenei c tolerance without toxic or myeloablative host conditioning are revie wed.