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Allografting

Allogeneic intra-BM-BMT plus adult thymus transplantation from same donor has benefits for long-term survival even after sublethal irradiation or low-dose BM cell injection

Bone Marrow Transplantation volume 43, pages 829–837 (2009)Cite this article

Abstract

We examined the effects of intra-BM-BMT (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor after 5.5 Gy sublethal irradiation (SubLI) or low-dose (3 × 106) BM cell injection (LDBMCI). With SubLI, BALB/c mice that had received 1 × 107 bone marrow cells by IBM-BMT plus ATT from B6 mice showed 73% donor chimerism, whereas those treated with IBM-BMT alone showed 45% chimerism. In the LDBMCI with 7Gy irradiation, IBM-BMT plus ATT resulted in a 90% survival rate with 90% chimerism, whereas IBM-BMT alone resulted in a 55% survival rate with 44% chimerism. Although the number of CD4 T cells was higher in IBM-BMT plus ATT than in IBM-BMT alone, the percentages of FoxP3+/CD4+ T cells and lymphocyte functions in the former were almost identical to those in the latter. When treated with IBM-BMT plus donor lymphocyte infusion (DLI), the mice showed a reduced survival time as a result of GVHD, with low numbers of FoxP3+CD4 T cells under either condition, although 100% chimerism was induced. These results suggest that IBM-BMT plus ATT is effective in reconstituting the recipients with donor-derived cells even after SubLI or LDBMCI.

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Abbreviations

ATT:

adult thymus transplantation

BMCs:

bone marrow cells

BMT:

bone marrow transplantation

DLI:

donor lymphocyte infusion

GVHD:

graft-versus-host disease

IBM:

intra-bone marrow

LDBMCI:

low–dose bone marrow cell injection

SubLI:

sublethal irradiation

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Acknowledgements

This study was supported by a grant from ‘Haiteku Research Center’ of the Ministry of Education, a grant from the ‘Millennium’ program of the Ministry of Education, Culture, Sports, Science and Technology, a grant from the ‘Science Frontier’ program of the Ministry of Education, Culture, Sports, Science and Technology, a grant from the ‘The 21st Century Center of Excellence (COE)’ program of the Ministry of Education, Culture, Sports, Science and Technology, a grant-in-aid for scientific research (B) 11470062, grants-in-aid for scientific research on priority areas (A)10181225 and (A)11162221 and Health and Labor Sciences research grants (Research on Human Genome, Tissue Engineering Food Biotechnology) and also a grant from the Department of Transplantation for Regeneration Therapy (Sponsored by Otsuka Pharmaceutical Company, Ltd), a grant from Molecular Medical Science Institute, Otsuka Pharmaceutical Co., Ltd., a grant from Japan Immunoresearch Laboratories Co., Ltd (JIMRO) and a research grant B from Kansai Medical University.We thank Ms Y Tokuyama and Ms A Kitajima for their technical assistance, and Mr Hilary Eastwick-Field and Ms K Ando for their help in the preparation of the manuscript.

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  1. T Nishida and N Hosaka: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Kansai Medical University, Osaka, Japan

    T Nishida, N Hosaka, T Takaki, T Miyake, W Cui, M Inaba & S Ikehara

  2. Department of Urology, Kansai Medical University, Osaka, Japan

    T Nishida, H Kinoshita & T Matsuda

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  1. T Nishida
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  2. N Hosaka
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Correspondence to S Ikehara.

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Nishida, T., Hosaka, N., Takaki, T. et al. Allogeneic intra-BM-BMT plus adult thymus transplantation from same donor has benefits for long-term survival even after sublethal irradiation or low-dose BM cell injection. Bone Marrow Transplant 43, 829–837 (2009). https://doi.org/10.1038/bmt.2008.396

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