Double-Negative T-Cells during Acute Human Immunodeficiency Virus and Simian Immunodeficiency Virus Infections and Following Early Antiretroviral Therapy Initiation

Viruses. 2024 Oct 14;16(10):1609. doi: 10.3390/v16101609.

Abstract

HIV infection significantly affects the frequencies and functions of immunoregulatory CD3+CD4-CD8- double-negative (DN) T-cells, while the effect of early antiretroviral therapy (ART) initiation on these cells remains understudied. DN T-cell subsets were analyzed prospectively in 10 HIV+ individuals during acute infection and following early ART initiation compared to 20 HIV-uninfected controls. In this study, 21 Rhesus macaques (RMs) were SIV-infected, of which 13 were assessed during acute infection and 8 following ART initiation four days post-infection. DN T-cells and FoxP3+ DN Treg frequencies increased during acute HIV infection, which was not restored by ART. The expression of activation (HLA-DR/CD38), immune checkpoints (PD-1/CTLA-4), and senescence (CD28-CD57+) markers by DN T-cells and DN Tregs increased during acute infection and was not normalized by ART. In SIV-infected RMs, DN T-cells remained unchanged despite infection or ART, whereas DN Treg frequencies increased during acute SIV infection and were not restored by ART. Finally, frequencies of CD39+ DN Tregs increased during acute HIV and SIV infections and remained elevated despite ART. Altogether, acute HIV/SIV infections significantly changed DN T-cell and DN Treg frequencies and altered their immune phenotype, while these changes were not fully normalized by early ART, suggesting persistent HIV/SIV-induced immune dysregulation despite early ART initiation.

Keywords: CD4−CD8− T-cells; acute HIV infection; acute SIV infection; double negative (DN) T-cells; early ART; regulatory T-cells (Tregs).

MeSH terms

  • Animals
  • Anti-Retroviral Agents / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • HIV Infections* / virology
  • Humans
  • Macaca mulatta*
  • Male
  • Simian Acquired Immunodeficiency Syndrome* / drug therapy
  • Simian Acquired Immunodeficiency Syndrome* / immunology
  • Simian Acquired Immunodeficiency Syndrome* / virology
  • Simian Immunodeficiency Virus* / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Viral Load

Substances

  • Anti-Retroviral Agents