Prevention of Transplant Rejection: Can Tolerance be Achieved with Immunosuppressive Treatment?

Successful solid organ transplantation is generally attributed to the increasingly precise ability of drugs to control rejection. However, it was recently shown that a few donor haematolymphoid cells can survive for decades in recipients of successful organ allografts, a phenomenon called microchimaerism. The association for decades of haematolymphoid chimaerism with allograft tolerance in experimental transplantation suggests that immunosuppressive drugs merely create a milieu that enables an allograft and its complement of passenger leucocytes to prime the recipient for graft acceptance.Exploitation of this concept requires a fundamental shift in the classical view of passenger leucocytes only as initiators of rejection. Microchimaerism has taught us that solid organ transplantation involves the transfer of two donor organ systems to the recipient: the allograft parenchyma and the donor haematolymphoid system in the form of donor stem cells contained within the passenger leucocyte compartment. Each has the potential to integrate with the corresponding recipient system and carry out normal physiological functions, such as immunological self definition. Resistance to initial integration by mature T cells requires some form of immunosuppression, but maintenance of donor immune system function will depend on renewable supply of cells, which can be provided by engrafted progenitors. Successful clinical application will depend on the development of low morbidity methods to enhance engraftment of donor haemopoietic stem cells.