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, i t was recently shown that a few donor haematolymphoid cells can surviv e for decades in recipients of successful organ allografts, a phenomen on called microchimaerism. The association for decades of haematolymph oid chimaerism with allograft tolerance in experimental transplantatio n suggests that immunosuppressive drugs merely create a milieu that en ables an allograft and its complement of passenger leucocytes to prime the recipient for graft acceptance. Exploitation of this concept requ ires a fundamental shift in the classical view of passenger leucocytes only as initiators of rejection. Microchimaerism has taught us that s olid organ transplantation involves the transfer of two donor organ sy stems to the recipient: the allograft parenchyma and the donor haemato lymphoid system in the form of donor stem cells contained within the p assenger leucocyte compartment. Each has the potential to integrate wi th the corresponding recipient system and carry our normal physiologic al functions, such as immunological self definition. Resistance to ini tial integration by mature T cells requires some form of immunosuppres sion, but maintenance of donor immune system function will depend on r enewable supply of cells, which can be provided by engrafted progenito rs. Successful clinical application will depend on the development of low morbidity methods to enhance engraftment of donor haemopoietic ste m cells.