title: Role for early-differentiated natural killer cells in infectious mononucleosis.
abstract: A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56(dim) NKG2A(+) immunoglobulin-like receptor(-) NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology and Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland;
authors.forename: Tarik
authors.initials: T
authors.lastname: Azzi
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology and Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland;
authors.forename: Anna
authors.initials: A
authors.lastname: Lünemann
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland;
authors.forename: Anita
authors.initials: A
authors.lastname: Murer
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology and Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland; Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan;
authors.forename: Seigo
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Solna, Sweden;
authors.forename: Vivien
authors.initials: V
authors.lastname: Béziat
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Solna, Sweden; Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Karl-Johan
authors.initials: KJ
authors.lastname: Malmberg
authors.affiliation: Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland; Emergency Department and.
authors.forename: Georg
authors.initials: G
authors.lastname: Staubli
authors.affiliation: Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland; Division of Otolaryngology, University Children's Hospital of Zurich, Zurich, Switzerland; and.
authors.forename: Claudine
authors.initials: C
authors.lastname: Gysin
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology and Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland;
authors.forename: Christoph
authors.initials: C
authors.lastname: Berger
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland;
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland; Institute of Surgical Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Obinna
authors.initials: O
authors.lastname: Chijioke
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology and Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland;
authors.forename: David
authors.initials: D
authors.lastname: Nadal
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000821:virology*; D019002:CD56 Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000821:virology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D055815:Young Adult
chemical_list: D019002:CD56 Antigen