title: Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells.
abstract: The goal of most vaccines is the induction of long-lived memory T and B cells capable of protecting the host from infection by cytotoxic mechanisms, cytokines and high-affinity antibodies. However, efforts to develop vaccines against major human pathogens such as HIV and HCV have not been successful, thereby highlighting the need for novel approaches to circumvent immunoregulatory mechanisms that limit the induction of protective immunity. Here, we show that mouse natural killer (NK) cells inhibit generation of long-lived virus-specific memory T- and B cells as well as virus-specific antibody production after acute infection. Mechanistically, NK cells suppressed CD4 T cells and follicular helper T cells (T(FH)) in a perforin-dependent manner during the first few days of infection, resulting in a weaker germinal centre (GC) response and diminished immune memory. We anticipate that innovative strategies to relieve NK cell-mediated suppression of immunity should facilitate development of efficacious new vaccines targeting difficult-to-prevent infections.
authors.affiliation: 1] Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, MLC 15012, Cincinnati, Ohio 45229, USA [2] Immunology Graduate Program, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7038, Cincinnati, Ohio 45229, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Rydyznski
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 368 Plantation Street, ASC9-2014E, Worcester, Massachusetts, 01605, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Daniels
authors.affiliation: Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, MLC 15012, Cincinnati, Ohio 45229, USA.
authors.forename: Erik P
authors.initials: EP
authors.lastname: Karmele
authors.affiliation: Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, MLC 15012, Cincinnati, Ohio 45229, USA.
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Brooks
authors.affiliation: Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, MLC 15012, Cincinnati, Ohio 45229, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Mahl
authors.affiliation: 1] Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, MLC 15012, Cincinnati, Ohio 45229, USA [2] Immunology Graduate Program, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7038, Cincinnati, Ohio 45229, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Moran
authors.affiliation: 1] Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, MLC 15012, Cincinnati, Ohio 45229, USA [2] Immunology Graduate Program, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7038, Cincinnati, Ohio 45229, USA.
authors.forename: Caimei
authors.initials: C
authors.lastname: Li
authors.affiliation: Program in Immunology and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01605, USA.
authors.forename: Rujapak
authors.initials: R
authors.lastname: Sutiwisesak
authors.affiliation: 1] Department of Pathology, University of Massachusetts Medical School, 368 Plantation Street, ASC9-2014E, Worcester, Massachusetts, 01605, USA [2] Program in Immunology and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01605, USA.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Welsh
authors.affiliation: 1] Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, MLC 15012, Cincinnati, Ohio 45229, USA [2] Immunology Graduate Program, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7038, Cincinnati, Ohio 45229, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Waggoner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001117:Arenaviridae Infections / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002849:Chromatography, Gas; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010948:Viral Plaque Assay
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines