Tolerance induction: hematopoietic chimerism

Although numerous experimental models to induce allograft tolerance have been reported, it has been difficult to translate these basic studies to clinical transplantation. However, successful induction of tolerance in HLA-mismatched kidney transplantation has recently been reported. In this review, recent progress in tolerance induction in preclinical (nonhuman primates) and clinical transplantation is summarized.

Among many clinical trials to induce renal allograft tolerance, success has so far been achieved only by combining donor bone marrow with organ transplantation. Induction of renal allograft tolerance by transient or durable mixed chimerism has been reported in HLA-matched or mismatched kidney transplant recipients. More recently, renal allograft tolerance by induction of full donor chimerism has also been reported using a more intensified preparative conditioning regimen.

Durable allograft tolerance has been achieved by induction of hematopoietic chimerism in clinical kidney transplantation, with outstanding long-term results in successful cases. However, these approaches have been associated with higher early complications than are seen following transplantation with conventional immunosuppression. Improvements in the consistency and safety of tolerance induction and extension of successful protocols to other organs will be the next steps in bringing tolerance to a wider range of clinical applications.