Bone marrow aplasia induced by passenger leukocytes from heart allografts

Objective. Organ allografts contain passenger leukocytes that are transferr ed to the recipient with the transplantation, but their functional relevanc e to the recipient's immune system is still controversial. Materials and Methods. To clarify the functional capacity of passenger leuk ocytes, we attempted to enhance their effect in rat heart allograft recipie nts by selective depletion of recipient leukocytes using a monoclonal antib ody (mAb) against a recipient-specific allotype of CD45 (RT7(a)). Results. Although antibody treatment of the recipient alone led to profound lymphopenia and reversible myelosuppression, additional transplantation of an major histocompatibility complex-incompatible heart graft from an RT7(b ) donor led to lethal aplastic anemia in the recipients. This lethal effect was completely abrogated by postoperative anti-CD3 treatment of the recipi ent and was partially abrogated or delayed by depletion of passenger leukoc ytes through additional anti-RT7(b) antibody treatment of the recipient or gamma -irradiation of the graft, Conclusions. The results suggest a role for both donor and recipient-type T cells for the induction of aplastic anemia in this model. The study shows that, under defined conditions, allogeneic passenger leukocytes in a heart graft can have a profound effect on the recipient's immune system and bone marrow, (C) 2001 International Society for Experimental Hematology. publish ed by Elsevier Science Inc.