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

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.