HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells

Cell Rep. 2019 Apr 2;27(1):142-153.e4. doi: 10.1016/j.celrep.2019.03.016.

Abstract

Even with sustained antiretroviral therapy, resting CD4+ T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8+ T cells recognize infected, non-activated CD4+ T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8+ T cells from HIV controllers mediate more effective immune recognition than CD8+ T cells from progressors. These results indicate that non-activated HIV-infected CD4+ T cells can be targeted by CD8+ T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir.

Keywords: HIV; HIV cure; HLA; cytotoxic T lymphocytes; elite controllers; granzyme; immunologic synapse; perforin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Disease Progression
  • HEK293 Cells
  • HIV Infections / immunology*
  • HIV Infections / pathology*
  • HIV Infections / therapy
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • HeLa Cells
  • Humans
  • Immunity, Cellular / physiology*
  • Lymphocyte Activation / physiology
  • Viral Load / drug effects
  • Viral Load / immunology
  • Virus Replication / physiology