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Chimerism

IL-2 does not enhance the conversion to complete donor chimerism following nonmyeloablative hematopoietic cell transplantation in dogs

Bone Marrow Transplantation volume 31, pages 1027–1031 (2003)Cite this article

Summary:

A dog model of stable mixed hematopoietic chimerism was established in which leukocyte-antigen-identical littermates receive nonmyeloablative total body irradiation before hematopoietic cell transplantation and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Unmodified donor lymphocyte infusion (DLI) into stable mixed chimeras failed to increase donor chimerism, while DLI from donors sensitized to recipient minor-histocompatibility antigens promptly converted all recipients to complete donor chimerism. This established a model for studying approaches to enhance the graft-versus-host (GVH)-effect, a potential surrogate for graft-versus-leukemia activity. We asked if interleukin-2 (IL-2) given after unmodified DLI could result in reliable conversion to complete donor chimerism. IL-2, 4 × 105 IU/kg/day, was administered to six mixed chimeric dogs for 14 days. Four dogs received unmodified DLI with IL-2. At 20–40 weeks after DLI, all dogs remained mixed chimeras. For the two recipients of IL-2 only, mixed chimerism also remained unchanged. These results show that IL-2 given with DLI after nonmyeloablative transplantation in dogs is not effective in reliably converting mixed to complete donor chimerism.

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Acknowledgements

We are grateful to the technicians of the Shared Canine Resource and the Hematology and Transplantation Biology Laboratories for their technical assistance. We gratefully acknowledge Dr John L Wagner, MD and James Works for DLA typing, and thank Benjamin Weigler, DVM, PhD, and Michelle Spector, DVM, who provided veterinary support. We are very grateful to Bonnie Larson, Helen Crawford, Lori Ausburn, Sue Carbonneau and Karen Carbonneau for their outstanding administrative support. We thank Dr Raymond Tesi and Leila Nawbatt, SangStat, Freemont, CA, for providing Cyclosporine (SangCya®, Cyclosporine Oral solution), Dr Sabine Hadulco, Roche Bioscience, Nutley, NJ, for providing mycophenolate mofetil, and Amgen Inc., Thousand Oaks, CA, for recombinant canine G-CSF. This work was supported in part by Grants DK02753, DK42716, HL63457, CA78902 awarded by the National Institutes of Health, DHHS, Bethesda, MD, USA. RS also received support from the Laura Landro Salomon Endowment Fund and a prize from the Josef Steiner Krebsstiftung, Bern, Switzerland. JMZ is a postdoctoral fellow from the Department of Hematology, University Medical School, Gdańsk, Poland, and is also a recipient of the International Fellowship for Young PhDs, awarded by the Foundation for Polish Science, Warsaw, Poland.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    G E Georges, R Storb, J Maciej Zaucha, A G Taranova, T Gooley & R A Nash

  2. Department of Medicine, University of Washington, Seattle, WA, USA

    G E Georges, R Storb & R A Nash

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  1. G E Georges
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Georges, G., Storb, R., Maciej Zaucha, J. et al. IL-2 does not enhance the conversion to complete donor chimerism following nonmyeloablative hematopoietic cell transplantation in dogs. Bone Marrow Transplant 31, 1027–1031 (2003). https://doi.org/10.1038/sj.bmt.1704046

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