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

R. Hanajiri, M. Murata, K. Sugimoto, M. Murase, R. Sakemura, T. Goto, K. Watanabe, N. Imahashi, S. Terakura, H. Ohashi, Yoshiki Akatsuka, S. Kurahashi, K. Miyamura, H. Kiyoi, T. Nishida, T. Naoe

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1187-1194
Number of pages8
JournalBone Marrow Transplantation
Volume50
Issue number9
DOIs
Publication statusPublished - 04-09-2015

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Graft Rejection
Fetal Blood
Allografts
Cytotoxic T-Lymphocytes
Cellular Immunity
Tissue Donors
Stem Cell Transplantation
Humoral Immunity
T-Lymphoid Precursor Cells
T-Lymphocytes
Enzyme-Linked Immunospot Assay
Isoantigens
Bone Marrow Cells
Interferons
Biomarkers
Observation
Transplants
HLA-B54 antigen

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Hanajiri, R., Murata, M., Sugimoto, K., Murase, M., Sakemura, R., Goto, T., ... Naoe, T. (2015). Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection. Bone Marrow Transplantation, 50(9), 1187-1194. https://doi.org/10.1038/bmt.2015.119
Hanajiri, R. ; Murata, M. ; Sugimoto, K. ; Murase, M. ; Sakemura, R. ; Goto, T. ; Watanabe, K. ; Imahashi, N. ; Terakura, S. ; Ohashi, H. ; Akatsuka, Yoshiki ; Kurahashi, S. ; Miyamura, K. ; Kiyoi, H. ; Nishida, T. ; Naoe, T. / Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection. In: Bone Marrow Transplantation. 2015 ; Vol. 50, No. 9. pp. 1187-1194.
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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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Hanajiri, R, Murata, M, Sugimoto, K, Murase, M, Sakemura, R, Goto, T, Watanabe, K, Imahashi, N, Terakura, S, Ohashi, H, Akatsuka, Y, Kurahashi, S, Miyamura, K, Kiyoi, H, Nishida, T & Naoe, T 2015, 'Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection', Bone Marrow Transplantation, vol. 50, no. 9, pp. 1187-1194. https://doi.org/10.1038/bmt.2015.119

Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection. / Hanajiri, R.; Murata, M.; Sugimoto, K.; Murase, M.; Sakemura, R.; Goto, T.; Watanabe, K.; Imahashi, N.; Terakura, S.; Ohashi, H.; Akatsuka, Yoshiki; Kurahashi, S.; Miyamura, K.; Kiyoi, H.; Nishida, T.; Naoe, T.

In: Bone Marrow Transplantation, Vol. 50, No. 9, 04.09.2015, p. 1187-1194.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection

AU - Hanajiri, R.

AU - Murata, M.

AU - Sugimoto, K.

AU - Murase, M.

AU - Sakemura, R.

AU - Goto, T.

AU - Watanabe, K.

AU - Imahashi, N.

AU - Terakura, S.

AU - Ohashi, H.

AU - Akatsuka, Yoshiki

AU - Kurahashi, S.

AU - Miyamura, K.

AU - Kiyoi, H.

AU - Nishida, T.

AU - Naoe, T.

PY - 2015/9/4

Y1 - 2015/9/4

N2 - 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.

AB - 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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