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 recipient's immune system is still controversial.


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 (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 recipient and was partially abrogated or delayed by depletion of passenger leukocytes 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.
Ko
S
S
Klinik für Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
Dahlke
M H
MH
Lauth
O
O
Jäger
M D
MD
Deiwick
A
A
Dinkel
A
A
Tsui
T
T
Wonigeit
K
K
Schlitt
H J
HJ
D000741:Anemia, Aplastic / Q000209:etiology* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001853:Bone Marrow / Q000473:pathology*; D005720:Gamma Rays; D006082:Graft Enhancement, Immunologic; D006087:Graft vs Host Reaction; D016027:Heart Transplantation / Q000009:adverse effects*; D006648:Histocompatibility; D007108:Immune Tolerance; D007518:Isoantibodies / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008212:Lymphocyte Depletion; D016853:Muromonab-CD3 / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000528:radiation effects / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000009:adverse effects*
D000911:Antibodies, Monoclonal; D007518:Isoantibodies; D016853:Muromonab-CD3; D017493:Leukocyte Common Antigens