Are donor lymphocytes a barrier to transplantation tolerance?

PURPOSE OF REVIEW: Following solid organ transplantation (SOT), populations of donor lymphocytes are frequently found in the recipient circulation. Their impact on host alloimmunity has long been debated but remains unclear, and it has been suggested that transferred donor lymphocytes may either promote tolerance to the graft or hasten its rejection. We discuss possible mechanisms by which the interaction of donor passenger lymphocytes with recipient immune cells may either augment the host alloimmune response or inhibit it.

RECENT FINDINGS: Recent work has highlighted that donor T lymphocytes are the most numerous of the donor leukocyte populations within a SOT and that these may be transferred to the recipient after transplantation. Surprisingly, graft-versus-host recognition of major histocompatibility complex class II on host B cells by transferred donor CD4 T cells can result in marked augmentation of host humoral alloimmunity and lead to early graft failure. Killing of donor CD4 T cells by host natural killer cells is critical in preventing this augmentation.

SUMMARY: The ability of passenger donor CD4 T cells to effect long-term augmentation of the host humoral alloimmune response raises the possibility that ex-vivo treatment or modification of the donor organ prior to implantation may improve long-term transplant outcomes.