title: MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: 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.
authors.forename: Hao-Wei
authors.initials: HW
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: 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.
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
authors.affiliation: 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.
authors.forename: Joji
authors.initials: J
authors.lastname: Fujisaki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D057054:Molecular Imaging; D014184:Transplantation, Homologous / Q000009:adverse effects; D014185:Transplantation, Isogeneic / Q000009:adverse effects
chemical_list: D015395:Histocompatibility Antigens Class I