NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs.
NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs.
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DOI：
10.1016/j.stemcr.2017.07.020
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发表时间：
2017-09-12
影响因子：
5.9
通讯作者：
Kawamoto H
中科院分区：
文献类型：
--
作者：
Ichise H;Nagano S;Maeda T;Miyazaki M;Miyazaki Y;Kojima H;Yawata N;Yawata M;Tanaka H;Saji H;Masuda K;Kawamoto H
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. Cells from HLA-homo iPSCs are killed by NK cells from an HLA-hetero C1/C2 individual NK cells kill the regenerated cells by sensing the lack of KIR ligand expression Cytotoxicity is cancelled when regenerated cells overexpress the missing KIR ligand In this article, Kawamoto and colleagues show that NK cells derived from an HLA-hetero individual killed the cells regenerated from HLA-homo iPSCs in KIR ligand-mismatched cases, by sensing the lack of KIR ligand expression. Such cytotoxicity was cancelled when regenerated cells are enforced to express the missing KIR ligand, providing a novel approach to prevent NK cell-mediated rejection.
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影响因子：
5.9
作者：
Sugita, Sunao;Iwasaki, Yuko;Makabe, Kenichi;Kamao, Hiroyuki;Mandai, Michiko;Shiina, Takashi;Ogasawara, Kazumasa;Hirami, Yasuhiko;Kurimoto, Yasuo;Takahashi, Masayo
通讯作者：
Takahashi, Masayo
影响因子：
--
作者：
Maxwell, LD;Wallace, A;Curran, MD
通讯作者：
Curran, MD
影响因子：
30.8
作者：
Norman, Paul J.;Abi-Rached, Laurent;Parham, Peter
通讯作者：
Parham, Peter
影响因子：
3.7
作者：
Nowak, Izabela;Majorczyk, Edyta;Kusnierczyk, Piotr
通讯作者：
Kusnierczyk, Piotr
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Tanabe, Koji;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya