TY - JOUR
T1 - Prolonged experimental CD4+ T-cell depletion does not cause disease progression in SIV-infected African green monkeys
AU - Le Hingrat, Quentin
AU - Sette, Paola
AU - Xu, Cuiling
AU - Rahmberg, Andrew R.
AU - Tarnus, Lilas
AU - Annapureddy, Haritha
AU - Kleinman, Adam
AU - Brocca-Cofano, Egidio
AU - Sivanandham, Ranjit
AU - Sivanandham, Sindhuja
AU - He, Tianyu
AU - Capreri, Daniel J.
AU - Ma, Dongzhu
AU - Estes, Jacob D.
AU - Brenchley, Jason M.
AU - Apetrei, Cristian
AU - Pandrea, Ivona
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85148718978&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85148718978&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-36379-2
DO - 10.1038/s41467-023-36379-2
M3 - Article
C2 - 36813761
AN - SCOPUS:85148718978
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 979
ER -