Bone marrow aplasia induced by passenger leukocytes from heart allografts

Exp Hematol. 2001 Mar;29(3):339-44. doi: 10.1016/s0301-472x(00)00676-7.

Abstract

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.

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 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Aplastic / etiology*
  • Anemia, Aplastic / immunology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Bone Marrow / pathology*
  • Gamma Rays
  • Graft Enhancement, Immunologic
  • Graft vs Host Reaction*
  • Heart Transplantation / adverse effects*
  • Histocompatibility
  • Immune Tolerance
  • Isoantibodies / immunology
  • Leukocyte Common Antigens / immunology
  • Lymphocyte Depletion
  • Muromonab-CD3 / pharmacology
  • Muromonab-CD3 / therapeutic use
  • Rats
  • Rats, Inbred Lew
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / radiation effects
  • T-Lymphocyte Subsets / transplantation*
  • Transplantation, Homologous / adverse effects*

Substances

  • Antibodies, Monoclonal
  • Isoantibodies
  • Muromonab-CD3
  • Leukocyte Common Antigens