title: Cutting Edge: Induction of Inflammatory Disease by Adoptive Transfer of an Atypical NK Cell Subset.
abstract: Several mouse models of systemic lupus erythematosus, including FcγRIIB-KO and TLR7tg mice, develop an expansion of an atypical NK cell subset with functional similarity to cells referred as IFN-producing killer DCs or pre-mature NKs in other systems. In this study, we show that atypical NKs purified from spleens of systemic lupus erythematosus-prone mice, and identified as NK1.1(+)CD11c(+)CD122(+)MHC-II(+), induce persistent autoimmune disease in an IFN-I- and CD40L-dependent manner when transferred to wild-type mice. A single transfer of 4 × 10(6) NK1.1(+) cells from TLR7tg into wild-type induces a 2-wk-long wave of inflammatory cytokines in the serum; a sustained increase in T cell activation and follicular helper cells for the following months; and a progressive expansion of dendritic cells, monocytes, and granulocytes. Furthermore, IL-15 deficiency, which impedes development of NK cells, ameliorates the autoimmune pathology of TLR7tg mice. These results suggest that cells of the NK lineage can develop into cytokine-producing/APCs that affect the priming and progression of systemic autoimmune disease.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Elisaveta
authors.initials: E
authors.lastname: Voynova
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Chen-Feng
authors.initials: CF
authors.lastname: Qi
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Bethany
authors.initials: B
authors.lastname: Scott
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 SBolland@niaid.nih.gov.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolland
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology*; D019409:Interleukin-15 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000235:genetics
chemical_list: D016207:Cytokines; C499172:Fcgr2b protein, mouse; D007370:Interferon Type I; D019409:Interleukin-15; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D023201:CD40 Ligand