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TRANSLATIONAL AND CLINICAL RESEARCH

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

^aFirst Department of Pathology,
^bDepartment of Surgery,
^cRegeneration Research Center for Intractable Diseases,
^dDepartment of Orthopedic Surgery,
^eThird Department of Internal Medicine,
^fDepartment of Emergency and Critical Care Medicine,
^gDepartment of Otolaryngology, Kansai Medical University, Osaka, Japan

Key Words. Intra-bone marrow • Bone marrow transplantation • Donor lymphocyte infusion • Graft-versus-host disease • Bone marrow stromal cells • Regulatory T cells • Helper T1/helper T2 polarization

Correspondence: Susumu Ikehara, M.D., Ph.D., 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; e-mail: ikehara{at}takii.kmu.ac.jp

Received on April 19, 2006; accepted for publication on March 9, 2007.

First published online in STEM CELLS EXPRESS  April 19, 2007.


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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				M. Inaba, Y. Adachi, H. Hisha, N. Hosaka, M. Maki, Y. Ueda, Y. Koike, T. Miyake, J. Fukui, Y. Cui, et al. Extensive Studies on Perfusion Method Plus Intra-Bone Marrow-Bone Marrow Transplantation Using Cynomolgus Monkeys Stem Cells, August 1, 2007; 25(8): 2098 - 2103. [Abstract] [Full Text] [PDF]