Microchimerism in promoting graft acceptance in clinical transplantation

Infusions of bone marrow-derived cells together with 'space making' continue to be tested in clinical organ transplant tolerance protocols. These trials are based on the hypothesis that this might produce initial multilineage chimerism. There is some evidence that this in turn induces regulatory cells that control alloimmunity. Although a wealth of knowledge is available from animal models, this review deals with what we know or can speculate about donor bone marrow cells and chimerism in human organ transplantation.

Calcineurin inhibitors are employed in most of these protocols to blunt the initial immune response. One protocol also has a stepwise regulatory cell generating treatment with sirolimus before total withdrawal. A number of donor chimeric lineages including stem cells, dendritic cells, myeloid precursors, and various lymphoid subpopulations have been described. Currently, it is recognized that the nature of cells that make up the chimerism could influence graft rejection versus acceptance. Tolerogenic donor chimeric cells may also generate regulatory subsets, thus controlling alloimmunity on two fronts.

It might be speculated that prolonged and sustained regulation or possible anergy induced by chimerism may eventually lead to clonal deletion, thereby bringing about classical immunologic tolerance.