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

研究成果: Contribution to journalArticle査読

34 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)853-867
ページ数15
ジャーナルStem Cell Reports
9
3
DOI
出版ステータス出版済み - 9 12 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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