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Prolonged experimental CD4+ T-cell depletion does not cause disease progression in SIV-infected African green monkeys

Author

Listed:
  • Quentin Le Hingrat

    (University of Pittsburgh
    University of Pittsburgh)

  • Paola Sette

    (University of Pittsburgh
    University of Pittsburgh)

  • Cuiling Xu

    (University of Pittsburgh
    University of Pittsburgh)

  • Andrew R. Rahmberg

    (Division of Intramural Research, NIAID, NIH)

  • Lilas Tarnus

    (University of Pittsburgh
    University of Pittsburgh)

  • Haritha Annapureddy

    (University of Pittsburgh)

  • Adam Kleinman

    (University of Pittsburgh)

  • Egidio Brocca-Cofano

    (University of Pittsburgh)

  • Ranjit Sivanandham

    (University of Pittsburgh)

  • Sindhuja Sivanandham

    (University of Pittsburgh)

  • Tianyu He

    (University of Pittsburgh)

  • Daniel J. Capreri

    (University of Pittsburgh)

  • Dongzhu Ma

    (University of Pittsburgh
    University of Pittsburgh)

  • Jacob D. Estes

    (Oregon Health & Science University
    Oregon Health & Science University)

  • Jason M. Brenchley

    (Division of Intramural Research, NIAID, NIH)

  • Cristian Apetrei

    (University of Pittsburgh
    University of Pittsburgh)

  • Ivona Pandrea

    (University of Pittsburgh
    University of Pittsburgh)

Abstract

CD4+ T-cell depletion is a hallmark of HIV infection, leading to impairment of cellular immunity and opportunistic infections, but its contribution to SIV/HIV-associated gut dysfunction is unknown. Chronically SIV-infected African Green Monkeys (AGMs) partially recover mucosal CD4+ T-cells, maintain gut integrity and do not progress to AIDS. Here we assess the impact of prolonged, antibody-mediated CD4 + T-cell depletion on gut integrity and natural history of SIV infection in AGMs. All circulating CD4+ T-cells and >90% of mucosal CD4+ T-cells are depleted. Plasma viral loads and cell-associated viral RNA in tissues are lower in CD4+-cell-depleted animals. CD4+-cell-depleted AGMs maintain gut integrity, control immune activation and do not progress to AIDS. We thus conclude that CD4+ T-cell depletion is not a determinant of SIV-related gut dysfunction, when gastrointestinal tract epithelial damage and inflammation are absent, suggesting that disease progression and resistance to AIDS are independent of CD4+ T-cell restoration in SIVagm-infected AGMs.

Suggested Citation

  • Quentin Le Hingrat & Paola Sette & Cuiling Xu & Andrew R. Rahmberg & Lilas Tarnus & Haritha Annapureddy & Adam Kleinman & Egidio Brocca-Cofano & Ranjit Sivanandham & Sindhuja Sivanandham & Tianyu He &, 2023. "Prolonged experimental CD4+ T-cell depletion does not cause disease progression in SIV-infected African green monkeys," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36379-2
    DOI: 10.1038/s41467-023-36379-2
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    References listed on IDEAS

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