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

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, Daniel J. Capreri, Dongzhu Ma, Jacob D. Estes, Jason M. Brenchley, Cristian Apetrei and Ivona Pandrea ()
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Quentin Le Hingrat: University of Pittsburgh
Paola Sette: University of Pittsburgh
Cuiling Xu: University of Pittsburgh
Andrew R. Rahmberg: Division of Intramural Research, NIAID, NIH
Lilas Tarnus: 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
Jacob D. Estes: Oregon Health & Science University
Jason M. Brenchley: Division of Intramural Research, NIAID, NIH
Cristian Apetrei: University of Pittsburgh
Ivona Pandrea: University of Pittsburgh

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36379-2

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