title: Impaired NK-cell education diminishes resistance to murine CMV infection.
abstract: Ly49G2 (G2+) NK cells mediate murine (M)CMV resistance in MHC D(k) -expressing mice. Bone marrow transplantation (BMT) studies revealed that G2+ NK cell-mediated MCMV resistance requires D(k) in both hematopoietic and nonhematopoietic cells. As a Ly49G2 ligand, D(k) in both cell lineages may contribute to lysis of virus-infected cells. Alternatively, cellular differences in self-MHC D(k) may have affected NK-cell education, and consequently NK cell-mediated viral clearance. We investigated the D(k) -licensing effect on BM-derived NK cells in BMT recipients by analyzing cytokines, cytotoxicity and MCMV resistance. In BMT recipients with lineage-restricted D(k) , G2+ NK-cell reactivity and cytotoxicity was diminished in comparison to BMT recipients with self-MHC in all cells. Reduced G2+ NK-mediated MCMV resistance in BMT recipients with lineage-restricted self-MHC indicates that licensing of G2+ NK cells is related to NK-cell reactivity and viral control. Titrating donor BM with self-MHC-bearing hematopoietic cells, as well as adoptive transfer of mature G2+ NK cells into BMT recipients with self-MHC in non-hematopoietic cells only, enhanced NK-cell licensing and rescued MCMV resistance. This disparate self-MHC NK-cell education model would suggest that inadequately licensed NK cells corresponded to inefficient viral sensing and clearance.
authors.affiliation: Department of Medicine, Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Hairong
authors.initials: H
authors.lastname: Wei
authors.forename: William T
authors.initials: WT
authors.lastname: Nash
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Makrigiannis
authors.forename: Michael G
authors.initials: MG
authors.lastname: Brown
mesh_terms: D016475:3T3 Cells; D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology*; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; C527095:Klra7 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A
keywords: Allogeneic transplantation; Ly49G2; MHC; NKp46