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. 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.

Automated summary

CD4(+) T-cell depletion does not determine SIV-related gut dysfunction or disease progression in SIV-infected African Green Monkeys. AGMs depleted of CD4(+) T-cells maintain gut integrity, control immune activation, and do not progress to AIDS. This suggests that disease progression and resistance to AIDS in AGMs are independent of CD4(+) T-cell restoration.