title: Human NK cell repertoire diversity reflects immune experience and correlates with viral susceptibility.
abstract: Innate natural killer (NK) cells are diverse at the single-cell level because of variegated expressions of activating and inhibitory receptors, yet the developmental roots and functional consequences of this diversity remain unknown. Because NK cells are critical for antiviral and antitumor responses, a better understanding of their diversity could lead to an improved ability to harness them therapeutically. We found that NK diversity is lower at birth than in adults. During an antiviral response to either HIV-1 or West Nile virus, NK diversity increases, resulting in terminal differentiation and cytokine production at the cost of cell division and degranulation. In African women matched for HIV-1 exposure risk, high NK diversity is associated with increased risk of HIV-1 acquisition. Existing diversity may therefore decrease the flexibility of the antiviral response. Collectively, the data reveal that human NK diversity is a previously undefined metric of immune history and function that may be clinically useful in forecasting the outcomes of infection and malignancy.
authors.affiliation: Stanford Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Dara M
authors.initials: DM
authors.lastname: Strauss-Albee
authors.affiliation: Department of Statistics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Fukuyama
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Liang
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06519, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Stanford Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Jarrell
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Drake
authors.affiliation: Department of Research and Programs, Kenyatta National Hospital, Nairobi 00202, Kenya.
authors.forename: John
authors.initials: J
authors.lastname: Kinuthia
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06519, USA.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Montgomery
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA 98195, USA. Department of Epidemiology, University of Washington, Seattle, WA 98195, USA. Department of Medicine, University of Washington, Seattle, WA 98195, USA. Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
authors.affiliation: Department of Statistics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Holmes
authors.affiliation: Stanford Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. cblish@stanford.edu.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Blish
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007630:Kenya; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D014019:Tissue Donors
chemical_list: D016207:Cytokines