title: Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals.
abstract: Long-lived "memory-like" NK cells have been identified in individuals infected by human cytomegalovirus (HCMV), but little is known about how the memory-like NK cell pool is formed. Here, we have shown that HCMV-infected individuals have several distinct subsets of memory-like NK cells that are often deficient for multiple transcription factors and signaling proteins, including tyrosine kinase SYK, for which the reduced expression was stable over time and correlated with epigenetic modification of the gene promoter. Deficient expression of these proteins was largely confined to the recently discovered FcRγ-deficient NK cells that display enhanced antibody-dependent functional activity. Importantly, FcRγ-deficient NK cells exhibited robust preferential expansion in response to virus-infected cells (both HCMV and influenza) in an antibody-dependent manner. These findings suggest that the memory-like NK cell pool is shaped and maintained by a mechanism that involves both epigenetic modification of gene expression and antibody-dependent expansion.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Ilwoong
authors.initials: I
authors.lastname: Hwang
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Ahrom
authors.initials: A
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Nitschke
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: MinJae
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Jeannine M
authors.initials: JM
authors.lastname: Scott
authors.affiliation: Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kamimura
authors.affiliation: Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Electronic address: kimsj@msu.edu.
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
mesh_terms: D000906:Antibodies / Q000276:immunology*; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000276:immunology*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000473:pathology / Q000821:virology; D046228:Microarray Analysis; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D000072377:Syk Kinase
chemical_list: D000906:Antibodies; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase