Chimerism and immunological tolerance in solid organ transplantation

In solid organ transplantation, chimerism inevitably occurs via the coexistence of donor-derived cells from the graft and host cells throughout the recipient. However, long-term immunosuppressive treatment is needed to suppress host immune responses to the foreign organ graft. The deliberate induction of stable mixed bone marrow chimerism to achieve donor-specific immunological tolerance in solid organ graft recipients is an ambitious goal that may significantly contribute to the long-term survival of solid organ grafts and their recipients. While this strategy has been effectively established in laboratory animals and some promising clinical case series have been reported, widespread clinical application is still limited by the toxicity of the necessary conditioning regimens. On the other hand, the naturally occurring chimeric state resulting from the bidirectional transplacental cell trafficking during pregnancy, the so-called feto-maternal microchimerism, can also induce immune tolerance and thus influence the outcome of mother-to-child or child-to-mother organ transplantation. This review provides an overview of the field's historical development, clinical results, and underlying principles of (micro) chimerism-based tolerance.