The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat

The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat

With an organ transplant, hematopoietic donor cells are transferred to the recipient. To study the relevance of the resulting microchimerism for allograft acceptance, we analyzed a rat model of cyclosporine-induced tolerance for strongly incompatible heart allografts. Using a monoclonal antibody tha...

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Bibliographic Details
Published in:Nature medicine Vol. 5; no. 11; pp. 1292 - 1297
Main Authors: Schlitt, Hans J, Ko, Saiho, Deiwick, Andrea, Jäger, Mark D, Dinkel, Astrid, Rohde, Frank, Fischer, Rainer, Tsui, Tung-Yu, Rittmann, Karl L, Wonigeit, Kurt
Format: Journal Article
Language:English
Published: United States 01-11-1999
Subjects:
Animals
Antibodies, Monoclonal - therapeutic use
Base Sequence
Cytokines - genetics
DNA Primers
Graft Survival - genetics
Graft Survival - immunology
Heart Transplantation - immunology
Leukocytes - immunology
Rats
Rats, Inbred Lew
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
Transplantation Chimera
Transplantation, Homologous
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Summary:With an organ transplant, hematopoietic donor cells are transferred to the recipient. To study the relevance of the resulting microchimerism for allograft acceptance, we analyzed a rat model of cyclosporine-induced tolerance for strongly incompatible heart allografts. Using a monoclonal antibody that detects a donor-specific CD45 allotype (RT7a), we selectively depleted donor leukocytes at different times after transplantation (days 0 or 18). Depletion was similarly effective at both times. However, only depletion on day 0 prevented tolerance induction and was associated with severe acute or chronic graft rejection. This indicates that passenger leukocytes have an essential immunomodulatory effect on the induction phase of allograft acceptance.
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ISSN:1078-8956
1546-170X
DOI:10.1038/15248