nk cell alloreactivity against kir-ligand-mismatched hla-haploidentical tissue derived from hla haplotype-homozygous ipscs

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ID: 148132
2017
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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.
Reference Key
ichise2017stemnk Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Hiroshi Ichise;Seiji Nagano;Takuya Maeda;Masaki Miyazaki;Yuki Miyazaki;Hiroto Kojima;Nobuyo Yawata;Makoto Yawata;Hidenori Tanaka;Hiroh Saji;Kyoko Masuda;Hiroshi Kawamoto
Journal nature reviews gastroenterology & hepatology
Year 2017
DOI
10.1016/j.stemcr.2017.07.020
URL
http://www.sciencedirect.com/science/article/pii/S2213671117303302
Keywords
transplantation ipscs regeneration nk cells vascular endothelial cells

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