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Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants

Author

Listed:
  • Sonwabile Dzanibe

    (University of Cape Town
    University of Cape Town)

  • Aaron J. Wilk

    (Stanford University)

  • Susan Canny

    (Stanford University
    Seattle Children’s Hospital)

  • Thanmayi Ranganath

    (Stanford University)

  • Berenice Alinde

    (Stellenbosch University)

  • Florian Rubelt

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Huang Huang

    (Stanford University School of Medicine)

  • Mark M. Davis

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University)

  • Susan P. Holmes

    (Stanford University)

  • Heather B. Jaspan

    (University of Cape Town
    University of Cape Town
    University of Washington)

  • Catherine A. Blish

    (Stanford University
    Stanford University School of Medicine
    Chan Zuckerberg Biohub)

  • Clive M. Gray

    (University of Cape Town
    Stellenbosch University)

Abstract

While preventing vertical HIV transmission has been very successful, HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to HIV-unexposed and uninfected infants (iHUU). Here we present a longitudinal multimodal analysis of infant immune ontogeny that highlights the impact of HIV/ARV exposure. Using mass cytometry, we show alterations in T cell memory differentiation between iHEU and iHUU being significant from week 15 of life. The altered memory T cell differentiation in iHEU was preceded by lower TCR Vβ clonotypic diversity and linked to TCR clonal depletion within the naïve T cell compartment. Compared to iHUU, iHEU had elevated CD56loCD16loPerforin+CD38+CD45RA+FcεRIγ+ NK cells at 1 month postpartum and whose abundance pre-vaccination were predictive of vaccine-induced pertussis and rotavirus antibody responses post 3 months of life. Collectively, HIV/ARV exposure disrupted the trajectory of innate and adaptive immunity from birth which may underlie relative vulnerability to infections in iHEU.

Suggested Citation

  • Sonwabile Dzanibe & Aaron J. Wilk & Susan Canny & Thanmayi Ranganath & Berenice Alinde & Florian Rubelt & Huang Huang & Mark M. Davis & Susan P. Holmes & Heather B. Jaspan & Catherine A. Blish & Clive, 2024. "Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47955-5
    DOI: 10.1038/s41467-024-47955-5
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    References listed on IDEAS

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