title: Rapid NK cell differentiation in a population with near-universal human cytomegalovirus infection is attenuated by NKG2C deletions.
abstract: Natural killer (NK) cells differentiate and mature during the human life course; human cytomegalovirus (HCMV) infection is a known driver of this process. We have explored human NK cell phenotypic and functional maturation in a rural African (Gambian) population with a high prevalence of HCMV. The effect of age on the frequency, absolute number, phenotype, and functional capacity of NK cells was monitored in 191 individuals aged from 1 to 49 years. Increasing frequencies of NK cells with age were associated with increased proportions of CD56dim cells expressing the differentiation marker CD57 and expansion of the NKG2C+ subset. Frequencies of NK cells responding to exogenous cytokines declined with age in line with a decreased proportion of CD57- cells. These changes coincided with a highly significant drop in anti-HCMV IgG titers by the age of 10 years, suggesting that HCMV infection is brought under control as NK cells differentiate (or vice versa). Deletion at the NKG2C locus was associated with a gene dose-dependent reduction in proportions of CD94+ and CD57+ NK cells. Importantly, anti-HCMV IgG titers were significantly elevated in NKG2C-/- children, suggesting that lack of expression of NKG2C may be associated with altered control of HCMV in childhood.
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom;
authors.forename: Martin R
authors.initials: MR
authors.lastname: Goodier
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom;
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: White
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council International Nutrition Group, Medical Research Council Keneba, Medical Research Council Unit, The Gambia;
authors.forename: Alansana
authors.initials: A
authors.lastname: Darboe
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom;
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Research and.
authors.forename: Adriana
authors.initials: A
authors.lastname: Goncalves
authors.affiliation: Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Bottomley
authors.affiliation: Medical Research Council International Nutrition Group, Medical Research Council Keneba, Medical Research Council Unit, The Gambia; Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Moore
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom;
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
mesh_terms: D000293:Adolescent; D000328:Adult; D018959:CD57 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics*; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism; D010641:Phenotype; D055815:Young Adult
chemical_list: D018959:CD57 Antigens; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D