[Transplant tolerance through mixed chimerism]

Three pilot studies have offered proof-of-concept that operational tolerance can be induced through mixed chimerism in recipients of combined kidney and hematopoietic cell transplants from the same donor. In two studies, sustained mixed chimerism was induced allowing safe and rejection-free immunosuppression withdrawal. However, this success came at heavy toll, requiring harsh cytoreductive regimen and a balance tipped toward graft-versus-host reactivity. Hence, achievement of durable chimerism in humans is not devoid of a significant risk of graft-versus-host disease. In contrast, transient mixed chimerism can be induced with non-myeloablative and a less cytotoxic regimen, leading to transplant tolerance, whose underpinning mechanisms are more complex, involving T cell exhaustion, peripheral deletion and suppression.