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

Nat Commun. 2023 Feb 22;14(1):979. doi: 10.1038/s41467-023-36379-2.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acquired Immunodeficiency Syndrome*
  • Animals
  • CD4-Positive T-Lymphocytes
  • Chlorocebus aethiops
  • Disease Progression
  • HIV Infections*
  • Simian Acquired Immunodeficiency Syndrome*
  • Simian Immunodeficiency Virus*