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Pre-Clinical Studies

Marrow graft rejection by repeated transfusions of allogeneic donor spleen cells

Bone Marrow Transplantation volume 40, pages 691–698 (2007)Cite this article

Abstract

Many hematological diseases require long-term transfusion support, which causes production of donor-reactive antibodies in sensitized recipients. Sensitized patients are at an increased risk for graft rejection when they undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we established a highly sensitized murine model to investigate the mechanism of donor graft rejection. After BALB/c mice were repeatedly transfused with allogeneic spleen cells from C57BL/6 mice, there was a significant increase in complement-dependent cytotoxicity in the serum of sensitized mice. For transplantation, 1 × 107 bone marrow cells (BMCs) from C57BL/6 mice were injected into lethally irradiated recipient BALB/c mice. Sensitized mice died between 12 and 15 days post-transplantation, while non-sensitized mice remained alive after 28 days. The hematopoietic recovery rate declined over time in sensitized recipients. The homing trace assay showed a rapid disappearance of donor BMCs in the spleen and bone marrow of sensitized recipients. In addition, the recipient cells and antibodies in the sensitized serum were capable of inducing high level of cell- and complement-mediated cytotoxicity to the donor graft. Our finding may explain the impaired hematopoietic stem cell homing and poor hematopoietic engraftment observed in highly sensitized allo-HSCT patients.

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Acknowledgements

We thank Jing Wei, Rong Bao and Yanfeng Wu for technical assistance. We also thank Leslie E Silberstein, Li Cai and Matthew Cohen for helpful discussion. This work was supported in part by Guangdong Natural Sciences Foundation 04009371, Guangdong Health Department Foundation A2005225, Guangdong Science and Technology Department Key Guiding Projects 2005 B30701010.

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Authors and Affiliations

  1. Department of Pediatrics, Second Affiliated Hospital of Zhongshan University, Guangzhou, PR China

    L H Xu, J P Fang, H G Xu & W J Weng

  2. Department of Experimental Animal Center, Zhongshan University, Guangzhou, PR China

    W G Huang

  3. Joint Program in Transfusion Medicine, Children's Hospital Boston and Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    G S Kao & Y Le

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  1. L H Xu
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Correspondence to J P Fang.

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Xu, L., Fang, J., Huang, W. et al. Marrow graft rejection by repeated transfusions of allogeneic donor spleen cells. Bone Marrow Transplant 40, 691–698 (2007). https://doi.org/10.1038/sj.bmt.1705791

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