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Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection

Bone Marrow Transplantation volume 50, pages 1187–1194 (2015)Cite this article

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Abstract

In allo-stem cell transplantation (SCT), it is unclear whether donor-specific anti-HLA Abs (DSAs) can actually mediate graft rejection or if they are simply surrogate markers for the cellular immunity that causes graft rejection. Here, we first analyzed a case of cord blood allograft rejection in which DSA and cytotoxic T lymphocyte (CTL) specific for donor HLA-B*54:01 were detected at the time of graft rejection. Both the DSA and CTL inhibited colony formation by unrelated bone marrow mononuclear cells sharing HLA-B*54:01, suggesting that the humoral and cellular immune responses were involved in the graft rejection. Interestingly, the DSA and CTL were also detected in cryopreserved pre-transplant patient blood, raising a hypothesis that the presence of anti-HLA Abs could be an indicator for corresponding HLA-specific T cells. We then evaluated the existence of HLA-specific CD8+ T cells in other patient blood specimens having anti-HLA class I Abs. Interferon-γ enzyme-linked immunospot assays clearly confirmed the existence of corresponding HLA-specific T-cell precursors in three of seven patients with anti-HLA Abs. In conclusion, our data demonstrate that integrated humoral and cellular immunity recognizing the same alloantigen of the donor can mediate graft rejection in DSA-positive patients undergoing HLA-mismatched allo-SCT. Further studies generalizing our observation are warranted.

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Acknowledgements

We thank Chika Wakamatsu and Yoko Matsuyama for their technical assistance. This work was supported in part by a grant (H25-Immunology-104 and H26-Immunology-106) from the Ministry of Health, Labor and Welfare, Japan and a Grant-in-Aid for Scientific Research (no. 23591415) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author contributions

RH and M Murata designed the study, performed the primary experiments, analyzed the data and wrote the paper. KS and M Murase prepared clinical samples, performed research and analyzed the data. RS, TG, KW, NI, HO and YA performed research. SK and KM prepared clinical samples. ST, HK, T Nishida and T Naoe contributed to the discussion and helped write the paper.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    R Hanajiri, M Murata, K Sugimoto, M Murase, R Sakemura, T Goto, K Watanabe, N Imahashi, S Terakura, H Kiyoi, T Nishida & T Naoe

  2. Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan

    H Ohashi

  3. Department of Hematology, School of Medicine, Fujita Health University, Toyoake, Japan

    Y Akatsuka

  4. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    S Kurahashi & K Miyamura

  5. National Hospital Organization, Nagoya Medical Center, Nagoya, Japan

    T Naoe

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  1. R Hanajiri
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Correspondence to M Murata.

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Hanajiri, R., Murata, M., Sugimoto, K. et al. Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection. Bone Marrow Transplant 50, 1187–1194 (2015). https://doi.org/10.1038/bmt.2015.119

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