Hirata Yuichi, Li Hao-Wei, Takahashi Kazuko, Ishii Hiroshi, Sykes Megan, Fujisaki Joji
Columbia Center for Translational Immunology, Department of Medicine, Surgery and Microbiology/Immunology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
PLoS One. 2015 Nov 6;10(11):e0141785. doi: 10.1371/journal.pone.0141785. eCollection 2015.
NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives. However, using high-resolution in vivo imaging, we demonstrated here that syngeneic MHC class I knockout (KO) donor HSPCs persist with the same survival frequencies as wild-type donor HSPCs. In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion. In vivo time-lapse imaging demonstrated that mice receiving allogeneic MHC class I KO HSPCs showed a significant increase in NK cell motility and proliferation as well as frequencies of NK cell contact with and killing of HSPCs as compared to mice receiving wild-type HSPCs. The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs.
自然杀伤（NK）细胞可抵抗缺乏主要组织相容性（MHC）I类分子的同基因和异基因骨髓（BM）细胞的植入，这表明供体MHC I类分子在防止NK细胞攻击供体造血干细胞和祖细胞（HSPC）及其衍生物方面起着关键作用。然而，通过高分辨率体内成像，我们在此证明同基因MHC I类敲除（KO）供体HSPC的存活频率与野生型供体HSPC相同。相比之下，同基因MHC I类KO分化造血细胞和异基因MHC I类KO HSPC以一种被NK细胞耗竭显著抑制的方式被排斥。体内延时成像显示，与接受野生型HSPC的小鼠相比，接受异基因MHC I类KO HSPC的小鼠的NK细胞运动性和增殖以及NK细胞与HSPC接触和杀伤的频率显著增加。数据表明，供体MHC I类分子是防止NK细胞介导的同基因分化细胞和异基因HSPC排斥所必需的，但不是同基因HSPC排斥所必需的。
