title: Expansion of a unique CD57⁺NKG2Chi natural killer cell subset during acute human cytomegalovirus infection.
abstract: During human CMV infection, there is a preferential expansion of natural killer (NK) cells expressing the activating CD94-NKG2C receptor complex, implicating this receptor in the recognition of CMV-infected cells. We hypothesized that NK cells expanded in response to pathogens will be marked by expression of CD57, a carbohydrate antigen expressed on highly mature cells within the CD56(dim)CD16(+) NK cell compartment. Here we demonstrate the preferential expansion of a unique subset of NK cells coexpressing the activating CD94-NKG2C receptor and CD57 in CMV(+) donors. These CD57(+)NKG2C(hi) NK cells degranulated in response to stimulation through their NKG2C receptor. Furthermore, CD57(+)NKG2C(hi) NK cells preferentially lack expression of the inhibitory NKG2A receptor and the inhibitory KIR3DL1 receptor in individuals expressing its HLA-Bw4 ligand. Moreover, in solid-organ transplant recipients with active CMV infection, the percentage of CD57(+)NKG2C(hi) NK cells in the total NK cell population preferentially increased. During acute CMV infection, the NKG2C(+) NK cells proliferated, became NKG2C(hi), and finally acquired CD57. Thus, we propose that CD57 might provide a marker of "memory" NK cells that have been expanded in response to infection.
authors.affiliation: Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco, CA 94143, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lopez-Vergès
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Milush
authors.forename: Brian S
authors.initials: BS
authors.lastname: Schwartz
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Pando
authors.forename: Jessica
authors.initials: J
authors.lastname: Jarjoura
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: York
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Houchins
authors.forename: Steve
authors.initials: S
authors.lastname: Miller
authors.forename: Sang-Mo
authors.initials: SM
authors.lastname: Kang
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Norris
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000378:metabolism; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D018959:CD57 Antigens / Q000096:biosynthesis / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology* / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000096:biosynthesis / Q000276:immunology*; D016377:Organ Transplantation; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D054341:Receptors, KIR3DL1 / Q000276:immunology / Q000378:metabolism; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D019002:CD56 Antigen; D018959:CD57 Antigens; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; C527059:KLRC2 protein, human; C522918:NCAM1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D017452:Receptors, IgG; D054341:Receptors, KIR3DL1