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Blood. 2014 Oct 16;124(16):2533-43. doi: 10.1182/blood-2014-01-553024. Epub 2014 Sep 9.

Role for early-differentiated natural killer cells in infectious mononucleosis.

Author information

1
Division of Infectious Diseases and Hospital Epidemiology and Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland;
2
Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland;
3
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;
4
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Solna, Sweden;
5
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;
6
Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland; Emergency Department and.
7
Children's Research Center, University Children's Hospital of Zurich, Zurich, Switzerland; Division of Otolaryngology, University Children's Hospital of Zurich, Zurich, Switzerland; and.
8
Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland; Institute of Surgical Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

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.

PMID:
25205117
PMCID:
PMC4199955
DOI:
10.1182/blood-2014-01-553024
[Indexed for MEDLINE]
Free PMC Article

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