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

Nature Medicine volume 5, pages 1292–1297 (1999)Cite this article

Abstract

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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Figure 1: In vivo effect of treatment with monoclonal antibody against RT7a on circulating RT7a-positive blood cells.
Figure 2: Serial analyses of peripheral blood microchimerism by PCR for a Y-chromosome marker.
Figure 3: Graft histology on day 200 after transplantation.
Figure 4: Cytokine mRNA expression in heart graft tissue on day 200, analyzed by quantitative RT–PCR.

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Acknowledgements

The authors thank L. Hänisch for animal care, M. Giesecke for microsurgical assistance and M.W. Hoffmann for critical review of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 265. S.K. was supported by a fellowship of the Alexander von Humboldt Stiftung; his present affiliation is First Department of Surgery, Nara Medical University, Kashihara, Nara 634, Japan.

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  1. Klinik für Viszeral-und Transplantationschirurgie, Medizinische Hochschule Hannover, Carl-Neuberg Strasse 1, Hannover, D-30623, Germany

    Saiho Ko, Andrea Deiwick, Mark D. Jäger, Astrid Dinkel, Frank Rohde, Rainer Fischer, Tung-Yu Tsui, Karl L. Rittmann, Kurt Wonigeit & Hans J. Schlitt

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  1. Saiho Ko
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Correspondence to Hans J. Schlitt.

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Ko, S., Deiwick, A., Jäger, M. et al. The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat. Nat Med 5, 1292–1297 (1999). https://doi.org/10.1038/15248

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