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IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques

Author

Listed:
  • Justin Harper

    (Emory University)

  • Nicolas Huot

    (Inflammation et Persistance)

  • Luca Micci

    (Emory University)

  • Gregory Tharp

    (Emory University)

  • Colin King

    (Emory University)

  • Philippe Rascle

    (Inflammation et Persistance
    Sorbonne Paris Cité)

  • Neeta Shenvi

    (Emory University)

  • Hong Wang

    (Emory University)

  • Cristin Galardi

    (University of North Carolina at Chapel Hill
    HIV Discovery, ViiV Healthcare)

  • Amit A. Upadhyay

    (Emory University)

  • Francois Villinger

    (University of Louisiana at Lafayette)

  • Jeffrey Lifson

    (Frederick National Laboratory for Cancer Research)

  • Guido Silvestri

    (Emory University
    Emory University School of Medicine)

  • Kirk Easley

    (Emory University)

  • Beatrice Jacquelin

    (Inflammation et Persistance)

  • Steven Bosinger

    (Emory University
    Emory University
    Emory University School of Medicine)

  • Michaela Müller-Trutwin

    (Inflammation et Persistance)

  • Mirko Paiardini

    (Emory University
    Emory University School of Medicine)

Abstract

Unlike HIV infection, which progresses to AIDS absent suppressive anti-retroviral therapy, nonpathogenic infections in natural hosts, such African green monkeys, are characterized by a lack of gut microbial translocation and robust secondary lymphoid natural killer cell responses resulting in an absence of chronic inflammation and limited SIV dissemination in lymph node B-cell follicles. Here we report, using the pathogenic model of antiretroviral therapy-treated, SIV-infected rhesus macaques that sequential interleukin-21 and interferon alpha therapy generate terminally differentiated blood natural killer cells (NKG2a/clowCD16+) with potent human leukocyte antigen-E-restricted activity in response to SIV envelope peptides. This is in contrast to control macaques, where less differentiated, interferon gamma-producing natural killer cells predominate. The frequency and activity of terminally differentiated NKG2a/clowCD16+ natural killer cells correlates with a reduction of replication-competent SIV in lymph node during antiretroviral therapy and time to viral rebound following analytical treatment interruption. These data demonstrate that African green monkey-like natural killer cell differentiation profiles can be rescued in rhesus macaques to promote viral clearance in tissues.

Suggested Citation

  • Justin Harper & Nicolas Huot & Luca Micci & Gregory Tharp & Colin King & Philippe Rascle & Neeta Shenvi & Hong Wang & Cristin Galardi & Amit A. Upadhyay & Francois Villinger & Jeffrey Lifson & Guido S, 2021. "IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23189-7
    DOI: 10.1038/s41467-021-23189-7
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    Cited by:

    1. Caroline Passaes & Delphine Desjardins & Anaïs Chapel & Valérie Monceaux & Julien Lemaitre & Adeline Mélard & Federico Perdomo-Celis & Cyril Planchais & Maël Gourvès & Nastasia Dimant & Annie David & , 2024. "Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Maria Pino & Amélie Pagliuzza & M. Betina Pampena & Claire Deleage & Elise G. Viox & Kevin Nguyen & Inbo Shim & Adam Zhang & Justin L. Harper & Sadia Samer & Colin T. King & Barbara Cervasi & Kiran P., 2022. "Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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