Molecular and cellular mechanisms of donor cell-induced tolerance

The induction of immunologic tolerance to solid organ allografts is a subject of intense investigation because of the morbidity and mortality associated with standard immunosuppressive therapy. One method that is currently in clinical and preclinical testing involves the transient ablation of recipient T cells using polyclonal antithymocyte sera or monoclonal anti-CD4/CD8 antibody treatment, followed by the posttransplant administration of donor bone marrow cells or of donor peripheral lymphoid populations. Recent studies in our laboratory have shown that the molecular and cellular basis of the prolongation of graft survival by donor cell administration depends on the cellular compartment from which the donor cells were derived. We provide here a brief review of these data followed by new data suggesting that the mode of peripheral and central selection is also dependent on the source from which the donor cells were derived.