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Separation of antileukemic effects from graft-versus-host disease in MHC-haploidentical murine bone marrow transplantation: participation of host immune cells

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Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects. In clinical studies of HLA-mismatched HSCT, strong GVL effects have been reported. In the present study, we addressed the mechanism of the GVL and GVH response using MHC-haploidentical murine bone marrow transplantation (BMT) models. Recipient BDF1 (H-2b/d) mice received T cell-depleted bone marrow and spleen cells from B6C3F1 (H-2b/k) or C57BL/6 (H-2b) mice with or without P815 mastocytoma cells (H-2d) after receiving lethal total body irradiation. B6C3F1 → BDF1 (hetero-to-hetero type) recipients showed more powerful antileukemic effects with less severe GVHD than C57BL/6 → BDF1 (parent-to-F1 type) recipients. Compared with C57BL/6 → BDF1 recipients, significantly higher in vitro cytotoxic activity against P815 cells was observed in B6C3F1 → BDF1 recipients. Significantly lower CXCR3 expression on donor T cells and higher interferon (IFN)-γ expression were considered to be associated with strong antileukemic effects with less severe GVHD in B6C3F1 → BDF1 recipients. Furthermore, host immune cells, especially natural killer cells and CD8+ T cells, were found to contribute remarkably to high IFN-γ production in B6C3F1 → BDF1 recipients. Thus, in MHC-haploidentical HSCT, host immune cells may change the balance between GVH and GVL response through IFN-γ production.

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Acknowledgments

We thank Kimiko Yamamoto, Hirotsugu Kubo and Hatsuka Seki for technical assistance and also Dr. Tsuyoshi Iwasaki for helpful comments.

Conflict of interest statement

The authors have no financial conflicts of interest.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Atsushi Satake, Takayuki Inoue, Yuki Taniguchi, Takehito Imado, Tatsuya Fujioka, Kazuhiro Ikegame, Satoshi Yoshihara, Katsuji Kaida, Hiroya Tamaki, Masaya Okada & Hiroyasu Ogawa

  2. Laboratory of Host Defenses, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan

    Shuji Kubo, Yunfeng Xu & Haruki Okamura

  3. Laboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan

    Marika Horiuchi, Hiroya Tamaki & Hiroyasu Ogawa

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  1. Atsushi Satake
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  2. Takayuki Inoue
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  9. Kazuhiro Ikegame
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  15. Hiroyasu Ogawa
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Correspondence to Hiroyasu Ogawa.

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Satake, A., Inoue, T., Kubo, S. et al. Separation of antileukemic effects from graft-versus-host disease in MHC-haploidentical murine bone marrow transplantation: participation of host immune cells. Int J Hematol 91, 485–497 (2010). https://doi.org/10.1007/s12185-010-0545-5

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  • DOI: https://doi.org/10.1007/s12185-010-0545-5

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