title: Neutrophils acquire the capacity for antigen presentation to memory CD4+T cells in vitro and ex vivo.
abstract: Neutrophils are critical cells of the innate immune system and rapidly respond to tissue injury and infection. Increasing evidence also indicates that neutrophils have versatile functions in contributing to adaptive immunity by internalizing and transporting antigen and influencing antigen-specific responses. Here, we demonstrate that freshly isolated human neutrophils can function as antigen-presenting cells (APCs) to memory CD4+T cells. Neutrophils pulsed with the cognate antigens cytomegalovirus pp65 or influenza hemagglutinin were able to present the antigens to autologous antigen-specific CD4+T cells in a major histocompatibility complex class II (MHC-II; HLA-DR)-dependent manner. Although myeloid dendritic cells and monocytes showed superior presenting ability, neutrophils consistently displayed antigen presentation capability. Upregulation of HLA-DR on neutrophils required the presence of the antigen-specific or activated T cells whereas exposure to innate stimuli such as Toll-like receptor ligands was not sufficient. Neutrophils sorted from vaccine-draining lymph nodes from rhesus macaques also showed expression of HLA-DR and were capable of presenting vaccine antigen to autologous antigen-specific memory CD4+T cells ex vivo. Altogether, the data demonstrate that neutrophils can adapt a function as APCs and, in combination with their abundance in the immune system, may have a significant role in regulating antigen-specific T-cell responses.
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna.|Center for Molecular Medicine, and.
authors.forename: Maria
authors.identifier: 0000-0003-4445-1834
authors.initials: M
authors.lastname: Vono
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna.|Center for Molecular Medicine, and.
authors.forename: Ang
authors.identifier: 0000-0001-5662-1576
authors.initials: A
authors.lastname: Lin
authors.affiliation: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Anna
authors.identifier: 0000-0001-9372-1795
authors.initials: A
authors.lastname: Norrby-Teglund
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna.|Center for Molecular Medicine, and.
authors.forename: Frank
authors.identifier: 0000-0001-8895-7381
authors.initials: F
authors.lastname: Liang
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna.|Center for Molecular Medicine, and.
authors.forename: Karin
authors.identifier: 0000-0001-7679-9494
authors.initials: K
authors.lastname: Loré
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa