Human natural killer cells mediate adaptive immunity to viral antigens

Rana Nikzad, Laura S. Angelo, Kevin Aviles-Padilla, Duy T. Le, Vipul K. Singh, Lynn Bimler, Milica Vukmanovic-Stejic, Elena Vendrame, Thanmayi Ranganath, Laura Simpson, Nancy Haigwood, Catherine A. Blish, Arne N. Akbar, Silke Paust

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    Adaptive immune responses are defined as antigen sensitization-dependent and antigen-specific responses leading to establishment of long-lived immunological memory. Although natural killer (NK) cells have traditionally been considered cells of the innate immune system, mounting evidence in mice and nonhuman primates warrants reconsideration of the existing paradigm that B and T cells are the sole mediators of adaptive immunity. However, it is currently unknown whether human NK cells can exhibit adaptive immune responses. We therefore tested whether human NK cells mediate adaptive immunity to virally encoded antigens using humanized mice and human volunteers. We found that human NK cells displayed vaccination-dependent, antigen-specific recall responses in vitro, when isolated from livers of humanized mice previously vaccinated with HIV-encoded envelope protein. Furthermore, we discovered that large numbers of cytotoxic NK cells with a tissue-resident phenotype were recruited to sites of varicella-zoster virus (VZV) skin test antigen challenge in VZV-experienced human volunteers. These NK-mediated recall responses in humans occurred decades after initial VZV exposure, demonstrating that NK memory in humans is long-lived. Our data demonstrate that human NK cells exhibit adaptive immune responses upon vaccination or infection. The existence of human memory NK cells may allow for the development of vaccination-based approaches capable of establishing potent NK-mediated memory functions contributing to host protection.

    Original languageEnglish (US)
    JournalScience immunology
    Volume4
    Issue number35
    DOIs
    StatePublished - May 10 2019

    Fingerprint

    Viral Antigens
    Adaptive Immunity
    Natural Killer Cells
    Human Herpesvirus 3
    Antigens
    Vaccination
    Volunteers
    Immunologic Memory
    Skin Tests
    Primates
    Immune System
    B-Lymphocytes
    HIV
    T-Lymphocytes
    Phenotype
    Liver

    ASJC Scopus subject areas

    • Immunology and Allergy

    Cite this

    Nikzad, R., Angelo, L. S., Aviles-Padilla, K., Le, D. T., Singh, V. K., Bimler, L., ... Paust, S. (2019). Human natural killer cells mediate adaptive immunity to viral antigens. Science immunology, 4(35). https://doi.org/10.1126/sciimmunol.aat8116

    Human natural killer cells mediate adaptive immunity to viral antigens. / Nikzad, Rana; Angelo, Laura S.; Aviles-Padilla, Kevin; Le, Duy T.; Singh, Vipul K.; Bimler, Lynn; Vukmanovic-Stejic, Milica; Vendrame, Elena; Ranganath, Thanmayi; Simpson, Laura; Haigwood, Nancy; Blish, Catherine A.; Akbar, Arne N.; Paust, Silke.

    In: Science immunology, Vol. 4, No. 35, 10.05.2019.

    Research output: Contribution to journalArticle

    Nikzad, R, Angelo, LS, Aviles-Padilla, K, Le, DT, Singh, VK, Bimler, L, Vukmanovic-Stejic, M, Vendrame, E, Ranganath, T, Simpson, L, Haigwood, N, Blish, CA, Akbar, AN & Paust, S 2019, 'Human natural killer cells mediate adaptive immunity to viral antigens', Science immunology, vol. 4, no. 35. https://doi.org/10.1126/sciimmunol.aat8116
    Nikzad R, Angelo LS, Aviles-Padilla K, Le DT, Singh VK, Bimler L et al. Human natural killer cells mediate adaptive immunity to viral antigens. Science immunology. 2019 May 10;4(35). https://doi.org/10.1126/sciimmunol.aat8116
    Nikzad, Rana ; Angelo, Laura S. ; Aviles-Padilla, Kevin ; Le, Duy T. ; Singh, Vipul K. ; Bimler, Lynn ; Vukmanovic-Stejic, Milica ; Vendrame, Elena ; Ranganath, Thanmayi ; Simpson, Laura ; Haigwood, Nancy ; Blish, Catherine A. ; Akbar, Arne N. ; Paust, Silke. / Human natural killer cells mediate adaptive immunity to viral antigens. In: Science immunology. 2019 ; Vol. 4, No. 35.
    @article{d0ab735855654473ac494c5256549c48,
    title = "Human natural killer cells mediate adaptive immunity to viral antigens",
    abstract = "Adaptive immune responses are defined as antigen sensitization-dependent and antigen-specific responses leading to establishment of long-lived immunological memory. Although natural killer (NK) cells have traditionally been considered cells of the innate immune system, mounting evidence in mice and nonhuman primates warrants reconsideration of the existing paradigm that B and T cells are the sole mediators of adaptive immunity. However, it is currently unknown whether human NK cells can exhibit adaptive immune responses. We therefore tested whether human NK cells mediate adaptive immunity to virally encoded antigens using humanized mice and human volunteers. We found that human NK cells displayed vaccination-dependent, antigen-specific recall responses in vitro, when isolated from livers of humanized mice previously vaccinated with HIV-encoded envelope protein. Furthermore, we discovered that large numbers of cytotoxic NK cells with a tissue-resident phenotype were recruited to sites of varicella-zoster virus (VZV) skin test antigen challenge in VZV-experienced human volunteers. These NK-mediated recall responses in humans occurred decades after initial VZV exposure, demonstrating that NK memory in humans is long-lived. Our data demonstrate that human NK cells exhibit adaptive immune responses upon vaccination or infection. The existence of human memory NK cells may allow for the development of vaccination-based approaches capable of establishing potent NK-mediated memory functions contributing to host protection.",
    author = "Rana Nikzad and Angelo, {Laura S.} and Kevin Aviles-Padilla and Le, {Duy T.} and Singh, {Vipul K.} and Lynn Bimler and Milica Vukmanovic-Stejic and Elena Vendrame and Thanmayi Ranganath and Laura Simpson and Nancy Haigwood and Blish, {Catherine A.} and Akbar, {Arne N.} and Silke Paust",
    year = "2019",
    month = "5",
    day = "10",
    doi = "10.1126/sciimmunol.aat8116",
    language = "English (US)",
    volume = "4",
    journal = "Science immunology",
    issn = "2470-9468",
    publisher = "American Association for the Advancement of Science",
    number = "35",

    }

    TY - JOUR

    T1 - Human natural killer cells mediate adaptive immunity to viral antigens

    AU - Nikzad, Rana

    AU - Angelo, Laura S.

    AU - Aviles-Padilla, Kevin

    AU - Le, Duy T.

    AU - Singh, Vipul K.

    AU - Bimler, Lynn

    AU - Vukmanovic-Stejic, Milica

    AU - Vendrame, Elena

    AU - Ranganath, Thanmayi

    AU - Simpson, Laura

    AU - Haigwood, Nancy

    AU - Blish, Catherine A.

    AU - Akbar, Arne N.

    AU - Paust, Silke

    PY - 2019/5/10

    Y1 - 2019/5/10

    N2 - Adaptive immune responses are defined as antigen sensitization-dependent and antigen-specific responses leading to establishment of long-lived immunological memory. Although natural killer (NK) cells have traditionally been considered cells of the innate immune system, mounting evidence in mice and nonhuman primates warrants reconsideration of the existing paradigm that B and T cells are the sole mediators of adaptive immunity. However, it is currently unknown whether human NK cells can exhibit adaptive immune responses. We therefore tested whether human NK cells mediate adaptive immunity to virally encoded antigens using humanized mice and human volunteers. We found that human NK cells displayed vaccination-dependent, antigen-specific recall responses in vitro, when isolated from livers of humanized mice previously vaccinated with HIV-encoded envelope protein. Furthermore, we discovered that large numbers of cytotoxic NK cells with a tissue-resident phenotype were recruited to sites of varicella-zoster virus (VZV) skin test antigen challenge in VZV-experienced human volunteers. These NK-mediated recall responses in humans occurred decades after initial VZV exposure, demonstrating that NK memory in humans is long-lived. Our data demonstrate that human NK cells exhibit adaptive immune responses upon vaccination or infection. The existence of human memory NK cells may allow for the development of vaccination-based approaches capable of establishing potent NK-mediated memory functions contributing to host protection.

    AB - Adaptive immune responses are defined as antigen sensitization-dependent and antigen-specific responses leading to establishment of long-lived immunological memory. Although natural killer (NK) cells have traditionally been considered cells of the innate immune system, mounting evidence in mice and nonhuman primates warrants reconsideration of the existing paradigm that B and T cells are the sole mediators of adaptive immunity. However, it is currently unknown whether human NK cells can exhibit adaptive immune responses. We therefore tested whether human NK cells mediate adaptive immunity to virally encoded antigens using humanized mice and human volunteers. We found that human NK cells displayed vaccination-dependent, antigen-specific recall responses in vitro, when isolated from livers of humanized mice previously vaccinated with HIV-encoded envelope protein. Furthermore, we discovered that large numbers of cytotoxic NK cells with a tissue-resident phenotype were recruited to sites of varicella-zoster virus (VZV) skin test antigen challenge in VZV-experienced human volunteers. These NK-mediated recall responses in humans occurred decades after initial VZV exposure, demonstrating that NK memory in humans is long-lived. Our data demonstrate that human NK cells exhibit adaptive immune responses upon vaccination or infection. The existence of human memory NK cells may allow for the development of vaccination-based approaches capable of establishing potent NK-mediated memory functions contributing to host protection.

    UR - http://www.scopus.com/inward/record.url?scp=85065937600&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85065937600&partnerID=8YFLogxK

    U2 - 10.1126/sciimmunol.aat8116

    DO - 10.1126/sciimmunol.aat8116

    M3 - Article

    C2 - 31076527

    AN - SCOPUS:85065937600

    VL - 4

    JO - Science immunology

    JF - Science immunology

    SN - 2470-9468

    IS - 35

    ER -