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Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection

Author

Listed:
  • Brendan T. Mann

    (Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University)

  • Marta Sanz

    (Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University)

  • Matthew L. Clohosey

    (University of North Carolina at Chapel Hill)

  • Kayley Langlands

    (School of Medicine and Health Sciences. George Washington University)

  • Alisha Chitrakar

    (Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University)

  • Carles Moreno-Soriano

    (Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University)

  • Joana Vitalle

    (Microbiology and Parasitology)

  • Marie Anne Iannone

    (University of North Carolina at Chapel Hill)

  • Ezequiel Ruiz-Mateos

    (Microbiology and Parasitology)

  • Claire Deleage

    (National Cancer Institute)

  • Marc Siegel

    (School of Medicine and Health Sciences. George Washington University)

  • Natalia Soriano-Sarabia

    (Immunology and Tropical Medicine. School of Medicine and Health Sciences. George Washington University)

Abstract

Curative strategies for human immunodeficiency virus (HIV-1) infection are hindered by incomplete characterization of the latent reservoir and limited enhancement of anti-HIV immune responses. In this study, we identify a dual role for peripheral and tissue-resident Vδ1 T cells within the gastrointestinal mucosa of virally suppressed people with HIV. Phenotypic analyses identify an increased frequency of highly differentiated, cytotoxic effector Vδ1 T cells that inhibit HIV-1 replication in vitro coinciding with increased degranulation and IFN-γ production. Conversely, we detect an enrichment of HIV-1 DNA in tissue-resident CD4 + Vδ1 T cells in situ. Despite low CD4 expression, we find circulating Vδ1 T cells also contain HIV-1 DNA which is replication-competent. We show that T cell receptor-mediated activation of peripheral Vδ1 T cells induces de novo upregulation of CD4 providing a plausible mechanism for increased permissibility to infection. These findings highlight juxtaposing roles for Vδ1 T cells in HIV-1 persistence including contribution to tissue reservoirs.

Suggested Citation

  • Brendan T. Mann & Marta Sanz & Matthew L. Clohosey & Kayley Langlands & Alisha Chitrakar & Carles Moreno-Soriano & Joana Vitalle & Marie Anne Iannone & Ezequiel Ruiz-Mateos & Claire Deleage & Marc Sie, 2025. "Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57260-4
    DOI: 10.1038/s41467-025-57260-4
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