Prevention of Graft-Versus-Host Disease by Intra-Bone Marrow Injection of Donor T Cells

Authors

  • Junichi Fukui,

    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Department of Surgery, Kansai Medical University, Osaka, Japan
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  • Muneo Inaba,

    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Regeneration Research Center for Intractable Diseases, Kansai Medical University, Osaka, Japan
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  • Yusuke Ueda,

    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Department of Orthopedic Surgery, Kansai Medical University, Osaka, Japan
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  • Takashi Miyake,

    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Department of Surgery, Kansai Medical University, Osaka, Japan
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  • Naoki Hosaka,

    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Regeneration Research Center for Intractable Diseases, Kansai Medical University, Osaka, Japan
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  • A-Hon Kwon,

    1. Department of Surgery, Kansai Medical University, Osaka, Japan
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  • Yutaku Sakaguchi,

    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
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  • Masanobu Tsuda,

    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan
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  • Mariko Omae,

    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Department of Otolaryngology, Kansai Medical University, Osaka, Japan
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  • Yasuo Kamiyama,

    1. Department of Surgery, Kansai Medical University, Osaka, Japan
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  • Susumu Ikehara M.D., Ph.D.

    Corresponding author
    1. First Department of Pathology, Kansai Medical University, Osaka, Japan
    2. Regeneration Research Center for Intractable Diseases, Kansai Medical University, Osaka, Japan
    • First Department of Pathology, Kansai Medical University, Fumizono-cho, Moriguchi City, Osaka, Japan, 570-8506. Telephone: +81-6-6992-1001 (ext. 2474 or 2475); Fax: +81-6-6992-1219
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Abstract

We have recently found that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to prevent graft-versus-host disease (GvHD), even when intensive donor lymphocyte infusion (DLI) is carried out. In the present study, in conjunction with IBM-BMT, allogeneic splenic T cells as DLI were also injected into the bone marrow cavity of lethally irradiated (8.5 Gy) recipients. The extent of GvHD was compared with that of recipients that had received allogeneic IBM-BMT plus i.v. injection of allogeneic T cells (intravenous DLI [IV-DLI]). GvHD in recipients treated with allogeneic IBM-BMT plus IBM-DLI was far milder than in those treated with allogeneic IBM-BMT plus IV-DLI. This was confirmed macroscopically and histopathologically. The frequency of regulatory T cells (Tregs) detected as CD4+CD25+ and CD4+Foxp3+ cells was significantly higher in recipients treated with IBM-BMT plus IBM-DLI than in those treated with IBM-BMT plus IV-DLI. Donor-derived helper T (Th) cells polarized to Th2 type in recipients treated with IBM-BMT plus IBM-DLI, whereas Th1 cells were dominant in recipients treated with IBM-BMT plus IV-DLI. Furthermore, the production of transforming growth factor-β and hepatocyte growth factor from bone marrow stromal cells was enhanced after IBM-DLI. Thus, IBM-BMT plus IBM-DLI seem to preferentially induce Tregs and Th2, resulting in the prevention of GvHD.

Disclosure of potential conflicts of interest is found at the end of this article.

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