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Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry

Author

Listed:
  • Mathieu Claireaux

    (Université de Paris
    CNRS UMR3569)

  • Rémy Robinot

    (Université de Paris
    CNRS UMR3569)

  • Jérôme Kervevan

    (Université de Paris
    CNRS UMR3569)

  • Mandar Patgaonkar

    (Université de Paris
    CNRS UMR3569)

  • Isabelle Staropoli

    (Université de Paris
    CNRS UMR3569)

  • Anne Brelot

    (Université de Paris
    CNRS UMR3569)

  • Alexandre Nouël

    (Université de Paris
    CNRS UMR3569)

  • Stacy Gellenoncourt

    (Université de Paris
    CNRS UMR3569)

  • Xian Tang

    (Université de Paris
    CNRS UMR3569)

  • Mélanie Héry

    (Université de Paris
    CNRS UMR3569)

  • Stevenn Volant

    (Université de Paris)

  • Emeline Perthame

    (Université de Paris)

  • Véronique Avettand-Fenoël

    (Laboratoire de Microbiologie clinique
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine)

  • Julian Buchrieser

    (Université de Paris
    CNRS UMR3569)

  • Thomas Cokelaer

    (Université de Paris
    Université de Paris)

  • Christiane Bouchier

    (Université de Paris)

  • Laurence Ma

    (Université de Paris)

  • Faroudy Boufassa

    (INSERM U1018, Center for Research in Epidemiology and Population Health (CESP))

  • Samia Hendou

    (INSERM U1018, Center for Research in Epidemiology and Population Health (CESP))

  • Valentina Libri

    (Université de Paris)

  • Milena Hasan

    (Université de Paris)

  • David Zucman

    (HIV Unit, Foch Hospital)

  • Pierre Truchis

    (Raymond Poincaré Hospital)

  • Olivier Schwartz

    (Université de Paris
    CNRS UMR3569)

  • Olivier Lambotte

    (INSERM U1184, Université Paris Sud, CEA, Center for Immunology of Viral Infections and Autoimmune Diseases
    University Hospital Paris Sud)

  • Lisa A. Chakrabarti

    (Université de Paris
    CNRS UMR3569)

Abstract

HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control.

Suggested Citation

  • Mathieu Claireaux & Rémy Robinot & Jérôme Kervevan & Mandar Patgaonkar & Isabelle Staropoli & Anne Brelot & Alexandre Nouël & Stacy Gellenoncourt & Xian Tang & Mélanie Héry & Stevenn Volant & Emeline , 2022. "Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28130-0
    DOI: 10.1038/s41467-022-28130-0
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