NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs

Hiroshi Ichise, Seiji Nagano, Takuya Maeda, Masaki Miyazaki, Yuki Miyazaki, Hiroto Kojima, Nobuyo Yawata, Makoto Yawata, Hidenori Tanaka, Hiroh Saji, Kyoko Masuda, Hiroshi Kawamoto

Research output: Contribution to journalArticle

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Abstract

HLA haplotype-homozygous (HLA-homo) induced pluripotent stem cells (iPSCs) are being prepared to be used for allogeneic transplantation of regenerated tissue into recipients carrying an identical haplotype in one of the alleles (HLA-hetero). However, it remains unaddressed whether natural killer (NK) cells respond to these regenerated cells. HLA-C allotypes, known to serve as major ligands for inhibitory receptors of NK cells, can be classified into group 1 (C1) and group 2 (C2), based on their binding specificities. We found that the T cells and vascular endothelial cells regenerated from HLA-homo-C1/C1 iPSCs were killed by specific NK cell subsets from a putative HLA-hetero-C1/C2 recipient. Such cytotoxicity was canceled when target cells were regenerated from iPSCs transduced with the C2 gene identical to the recipient. These results clarify that NK cells can kill regenerated cells by sensing the lack of HLA-C expression and further provide the basis for an approach to prevent such NK cell-mediated rejection responses.

Original languageEnglish
Pages (from-to)853-867
Number of pages15
JournalStem Cell Reports
Volume9
Issue number3
DOIs
Publication statusPublished - Sep 12 2017

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Induced Pluripotent Stem Cells
Stem cells
Natural Killer Cells
HLA-C Antigens
Haplotypes
Tissue
Ligands
Natural Killer Cell Receptors
T-cells
Endothelial cells
Cytotoxicity
Homologous Transplantation
Genes
Endothelial Cells
Alleles
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs. / Ichise, Hiroshi; Nagano, Seiji; Maeda, Takuya; Miyazaki, Masaki; Miyazaki, Yuki; Kojima, Hiroto; Yawata, Nobuyo; Yawata, Makoto; Tanaka, Hidenori; Saji, Hiroh; Masuda, Kyoko; Kawamoto, Hiroshi.

In: Stem Cell Reports, Vol. 9, No. 3, 12.09.2017, p. 853-867.

Research output: Contribution to journalArticle

Ichise, H, Nagano, S, Maeda, T, Miyazaki, M, Miyazaki, Y, Kojima, H, Yawata, N, Yawata, M, Tanaka, H, Saji, H, Masuda, K & Kawamoto, H 2017, 'NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs', Stem Cell Reports, vol. 9, no. 3, pp. 853-867. https://doi.org/10.1016/j.stemcr.2017.07.020
Ichise, Hiroshi ; Nagano, Seiji ; Maeda, Takuya ; Miyazaki, Masaki ; Miyazaki, Yuki ; Kojima, Hiroto ; Yawata, Nobuyo ; Yawata, Makoto ; Tanaka, Hidenori ; Saji, Hiroh ; Masuda, Kyoko ; Kawamoto, Hiroshi. / NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs. In: Stem Cell Reports. 2017 ; Vol. 9, No. 3. pp. 853-867.
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