학술논문
Prolonged experimental CD4+ T-cell depletion does not cause disease progression in SIV-infected African green monkeys
Document Type
Original Paper
Author
Le Hingrat, Quentin; Sette, Paola; Xu, Cuiling; Rahmberg, Andrew R.; Tarnus, Lilas; Annapureddy, Haritha; Kleinman, Adam; Brocca-Cofano, Egidio; Sivanandham, Ranjit; Sivanandham, Sindhuja; He, Tianyu; Capreri, Daniel J.; Ma, Dongzhu; Estes, Jacob D.; Brenchley, Jason M.; Apetrei, Cristian; Pandrea, Ivona
Source
Nature Communications. 14(1)
Subject
Language
English
ISSN
2041-1723
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.
HIV infection results in the depletion of CD4+ T cells overtime and the loss of coordinated cellular immunity, but how this corresponds to the SIV infected African Green Monkey (AGM) model of non-progressive disease is not known. Here the authors assess the impact of experimental CD4+ T cell depletion in AGM and show that lack of disease progression and resistance to AIDS in this model are independent of CD4+ T cell loss.
HIV infection results in the depletion of CD4