Bone marrow aplasia induced by passenger leukocytes from heart allografts

Objective Organ allografts contain passenger leukocytes that are transferred to the recipient with the transplantation, but their functional relevance to the recipientʹs immune system is still controversial. Materials and Methods To clarify the functional capacity of passenger leukocytes, we attempted to enhance their effect in rat heart allograft recipients by selective depletion of recipient leukocytes using a monoclonal antibody (mAb) against a recipient-specific allotype of CD45 (RT7a). 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 RT7b donor led to lethal aplastic anemia in the recipients. This lethal effect was completely abrogated by postoperative anti-CD3 treatment of the recipient and was partially abrogated or delayed by depletion of passenger leukocytes through additional anti-RT7b antibody treatment of the recipient or γ-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 recipientʹs immune system and bone marrow.