Tolerance in Solid-Organ Transplant

Immunotolerance, which is nonimmunologic reactivity to specific tissue, was demonstrated in animals in the 1950s. However, despite assiduous efforts, it has not been reproduced in human solid-organ transplant to date. Fortuitously, clinical operational tolerance, which is stable graft function for > 1 year with no immunosuppression, has been demonstrated, primarily in a few nonadherent recipients of kidney and liver transplant. Vigorous efforts to identify a biomarker to distinguish recipients with clinical operational tolerance from nontolerant recipients have so far not been successful. However, weaning of immunosuppression in stable pediatric and adult liver transplant recipients has been successful in 60% and 20% of recipients. In kidney transplant recipients, clinical operational tolerance has been induced by combined kidney and hematopoietic cell transplant to induce chimerism and subsequent weaning of immunosuppression. Recently, the ex vivo expansion of autologous regulatory T cells with subsequent infusion has facilitated weaning of immuno suppression in liver transplant recipients. Protocols have been initiated to expand the use of regulatory T cells to kidney transplant recipients. These new methodologies have the potential to induce clinical operational tolerance in all recipients of a solid-organ transplant in the future, thus avoiding the long-term consequences of continued dependence on immunosuppressive medications for stable graft function.