Exposure of Resting Peripheral Blood T Cells to HIV-1 Particles Generates CD25+ Killer Cells in a Small Subset, Leading to Induction of Apoptosis in Bystander Cells

Int Immunol. 1997 Oct;9(10):1453-62. doi: 10.1093/intimm/9.10.1453.

Abstract

Apoptosis is a major mechanism whereby HIV-1 depletes uninfected CD4+ and CD8+ T cells. We previously showed that resting peripheral blood T cells derived from healthy donors were killed by an apoptotic mechanism after adsorption to gp120-containing, protease-defective HIV-1 (L-2) particles, more effectively than parental wild-type LAI adsorption or rgp 120-mediated CD4 cross-linking, followed by mitogenic stimulation. Here, we present evidence that the L-2 particle-based apoptosis was induced both in CD4+ and CD8+ cells by generation of effector cells which were mainly derived from a resting memory CD4+CD38- subset. This subset enhanced the CD25 expression on the surface and secreted IFN-gamma in the culture supernatant after L-2 particle exposure. Significant elevation of Fas ligand mRNA was found in the subset by L-2 particle exposure, while expression of Fas antigen on uninfected T cells was induced by exposure to IFN-gamma. These results indicate that L-2 particles can shift the CD4+CD38- subpopulation from a resting to an activated state, and this activation leads to killing of bystander CD4+ and CD8+ T cells by a Fas-mediated mechanism. In fact, purified CD4+CD38- cells exposed to L-2 particles were converted into effector cells that were able to kill autologous as well as allogenic target T cells pretreated with IFN-gamma. Further, we found that the observation of apoptosis due to L-2 particles was a more general phenomenon, that also occurred with Thai primary HIV-1 isolates. These results suggest that such specific types of HIV-1 particles may play a major role in the induction of apoptosis for both bystander CD4+ and CD8+ T cells, through inappropriate activation of CD4+CD38- cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cytotoxicity, Immunologic
  • DNA Primers / genetics
  • Defective Viruses / immunology
  • Fas Ligand Protein
  • HIV Infections / blood
  • HIV Infections / etiology
  • HIV Infections / immunology
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity*
  • Humans
  • In Vitro Techniques
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Membrane Glycoproteins / genetics
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-2 / blood
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • DNA Primers
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Interleukin-2