title: Mouse host unlicensed NK cells promote donor allogeneic bone marrow engraftment.
abstract: Natural killer (NK) cells exist as subsets based on expression of inhibitory receptors that recognize major histocompatibility complex I (MHCI) molecules. NK cell subsets bearing MHCI binding receptors for self-MHCI have been termed as "licensed" and exhibit a higher ability to respond to stimuli. In the context of bone marrow transplantation (BMT), host licensed-NK (L-NK) cells have also been demonstrated to be responsible for the acute rejection of allogeneic and MHCI-deficient BM cells (BMCs) in mice after lethal irradiation. However, the role of recipient unlicensed-NK (U-NK) cells has not been well established with regard to allogeneic BMC resistance. After NK cell stimulation, the prior depletion of host L-NK cells resulted in a marked increase of donor engraftment compared with the untreated group. Surprisingly, this increased donor engraftment was reduced after total host NK cell depletion, indicating that U-NK cells can actually promote donor allogeneic BMC engraftment. Furthermore, direct coculture of U-NK cells with allogeneic but not syngeneic BMCs resulted in increased colony-forming unit cell growth in vitro, which was at least partially mediated by granulocyte macrophage colony-stimulating factor (GM-CSF) production. These data demonstrate that host NK cell subsets exert markedly different roles in allogeneic BMC engraftment where host L- and U-NK cells reject or promote donor allogeneic BMC engraftment, respectively.
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA;
authors.forename: Maite
authors.identifier: http://orcid.org/0000-0002-5969-9181
authors.initials: M
authors.lastname: Alvarez
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA; Department of Hematology, Henan Provincial People's Hospital and Zhengzhou University People's Hospital, Henan, China; and.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA; Department of Internal Medicine, University of California, Davis, Sacramento, CA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I; D016173:Macrophage Colony-Stimulating Factor; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse