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Graft-Versus-Tumor Effects

Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response

Bone Marrow Transplantation volume 34, pages 703–709 (2004)Cite this article

Summary:

The immune system of females is capable of recognizing and reacting against the male-specific minor histocompatibility antigen (mHA), HY. Thus, cytotoxic T-lymphocytes (CTLs) recognizing this antigen may be useful in eradicating leukemic cells of a male patient if they can be generated in vivo or in vitro from a human leukocyte antigen (HLA)-identical female donor. The HLA-A*0201-restricted HY antigen, FIDSYICQV, is a male-specific mHA. Using HLA-A2/HY peptide tetrameric complexes, we reveal a close association between the emergence of HY peptide-specific CD8+ T cells in peripheral blood and molecular remission of relapsed BCR/ABL+ chronic myelogenous leukemia in lymphoid blast crisis in a patient who underwent female-to-male transplantation. Assessment of intracellular cytokine levels identified T cells that produce interferon-γ in response to the HY peptide during the presence of HY tetramer-positive T cells. These results indicate that transplant with allogeneic HY-specific CTLs has therapeutic potential for relapsed leukemia, and that expansion of such T cells may be involved in the development of a graft-versus-leukemia response against lymphoblastic leukemia cells.

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor and Welfare. We wish to thank Megumi Yoshii for the excellent technical assistance as well as her patience in preparation of the manuscript.

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Authors and Affiliations

  1. Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    A Takami, C Sugimori, X Feng, Y Kondo, T Kotani, H Asakura, S Shiobara & S Nakao

  2. Department of Pediatrics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    A Yachie & R Nishimura

  3. Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan

    K Kuzushima

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  1. A Takami
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  2. C Sugimori
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  3. X Feng
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  4. A Yachie
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  10. S Shiobara
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  11. S Nakao
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Correspondence to A Takami.

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Takami, A., Sugimori, C., Feng, X. et al. Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response. Bone Marrow Transplant 34, 703–709 (2004). https://doi.org/10.1038/sj.bmt.1704583

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  • DOI: https://doi.org/10.1038/sj.bmt.1704583

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