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Cited by 278Immune Cell Function and InteractionHIV Research and TreatmentImmune responses and vaccinations

Antigen-specific NK cell memory in rhesus macaques

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Reeves, R Keith, Li, Haiying, Jost, Stephanie, Blass, Eryn, Li, Hualin, Schafer, Jamie L, Varner, Valerie, Manickam, Cordelia +4 more·2015·Nature Immunology
DOI 10.1038/ni.3227PMC PMC4545390
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Abstract

Natural killer (NK) cells have traditionally been considered nonspecific components of innate immunity, but recent studies have shown features of antigen-specific memory in mouse NK cells. However, it has remained unclear whether this phenomenon also exists in primates. We found that splenic and hepatic NK cells from SHIV(SF162P3)-infected and SIV(mac251)-infected macaques specifically lysed Gag- and Env-pulsed dendritic cells in an NKG2-dependent fashion, in contrast to NK cells from uninfected macaques. Moreover, splenic and hepatic NK cells from Ad26-vaccinated macaques efficiently lysed antigen-matched but not antigen-mismatched targets 5 years after vaccination. These data demonstrate that robust, durable, antigen-specific NK cell memory can be induced in primates after both infection and vaccination, and this finding could be important for the development of vaccines against HIV-1 and other pathogens.

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  • Studies on human livers have demonstrated selective expansion of a CD94/NKGC2 pos NK subset upon re-exposure to cytomegalovirus, possessing the ability to produce more IFNγ when exposed to the virus for a second time.

    “Studies on human livers have demonstrated the selective expansion of a CD94/NKGC2 pos NK subset upon re-exposure to cytomegalovirus, possessing the ability to produce more IFNγ when exposed to the virus for a second time.(75-77)”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [77]

    The Discussion (page unavailable) reports that NKG2C-expressing human NK cells expand in response to HCMV. It does not place those cells in human livers or report expansion on re-exposure or increased IFNγ production after a second exposure. The paper’s own memory experiments concern rhesus macaques. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • A subset of liver resident NK (lrNK) has been shown to retain a grade of antigen specificity, called 'memory-like NKs'.

    “Intriguingly, a subset of liver resident NK (lrNK) has been shown to retain a grade of antigen specificity. This subset has been called 'memory-like NKs'.”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [77]

    The Abstract (page not provided) reports antigen-specific memory mediated by a subset of liver-restricted NK cells in mice. But the Discussion uses ‘memory-like’ for a human NKG2C-positive subpopulation, not specifically for those liver-restricted cells; the paper does not establish that the two are the same subset. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Reeves, R. K., Li, H., Jost, S., Blass, E., Li, H., Schafer, J. L., Varner, V., Manickam, C., Eslamizar, L., Altfeld, M., von Andrian, U. H., & Barouch, D. H.
Affiliations
  • Beth Israel Deaconess Medical Center (US)
  • Harvard University (US)
Corresponding author
  • Reeves, R Keith
  • Barouch, Dan H
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2015-07-20
Volume
16
Issue
9
Pages
927-932
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.3227
PMC
PMC4545390
OpenAlex
W1878895776
Cited by
278
References
50
Citations by year
2026: 11 · 2025: 18 · 2024: 16 · 2023: 28 · 2022: 13 · 2021: 21 · 2020: 35 · 2019: 25 · 2018: 35 · 2017: 30 · 2016: 37 · 2015: 9
FWCI
16.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
National Institute of Allergy and Infectious Diseases (AI118468, AI067031, AI112521, F32AI009585, AI111595, R21AI118468, R01AI069259, AI060354, R01AI067031, R01AI111595, AI096040, AI095985, U19AI095985, R56AI120828, AI-069259, P01AI112521, U19AI078526, U19AI096040, P30AI060354, AI078526)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
natural killer cells, rhesus monkeys, HIV-1 vaccine, dendritic cells, long-term memory, innate immunity
MeSH terms
Animals, Dendritic Cells, Immunologic Memory, Killer Cells, Natural, Liver, Macaca mulatta, Spleen, Simian Immunodeficiency Virus, HIV-1, Simian Acquired Immunodeficiency Syndrome, AIDS Vaccines, Receptors, NK Cell Lectin-Like

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