CD8+ T cells promote HIV latency by remodeling CD4+ T cell metabolism to enhance their survival, quiescence, and stemness

Immunity. 2023 May 9;56(5):1132-1147.e6. doi: 10.1016/j.immuni.2023.03.010. Epub 2023 Apr 7.


HIV infection persists during antiretroviral therapy (ART) due to a reservoir of latently infected cells that harbor replication-competent virus and evade immunity. Previous ex vivo studies suggested that CD8+ T cells from people with HIV may suppress HIV expression via non-cytolytic mechanisms, but the mechanisms responsible for this effect remain unclear. Here, we used a primary cell-based in vitro latency model and demonstrated that co-culture of autologous activated CD8+ T cells with HIV-infected memory CD4+ T cells promoted specific changes in metabolic and/or signaling pathways resulting in increased CD4+ T cell survival, quiescence, and stemness. Collectively, these pathways negatively regulated HIV expression and ultimately promoted the establishment of latency. As shown previously, we observed that macrophages, but not B cells, promoted latency in CD4+ T cells. The identification of CD8-specific mechanisms of pro-latency activity may favor the development of approaches to eliminate the viral reservoir in people with HIV.

Keywords: CD8 T cells; CD8 suppression; HIV; HIV cure; HIV latency; HIV reservoir; T cell biology.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • HIV Infections*
  • Humans
  • Virus Latency
  • Virus Replication