Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4

Nature. 1998 Sep 10;395(6698):189-94. doi: 10.1038/26026.


CD8-positive T cells are thought to play an important role in the control of infection by human immunodeficiency virus (HIV) as a result of their cytotoxic activity and by releasing soluble factors. In AIDS patients, the absolute number of CD8+ T lymphocytes is decreased in peripheral blood and their turnover rate is increased, suggesting that there is more cell renewal and cell death occurring. Anti-retroviral therapy raises CD8+ T-cell counts in HIV-infected patients. Here we report that the death rate of CD8+ T cells by apoptosis increased markedly during HIV infection of peripheral blood mononuclear cells in vitro. Apoptosis is induced in a dose-dependent manner by recombinant envelope glycoprotein gp120 from HIV strain X4, or by stromal-derived factor-1 (SDF-1), the physiological ligand of the chemokine receptor CXCR4. Apoptosis is mediated by the interaction between tumour-necrosis factor-alpha bound to the membrane of macrophages (mbTNF) and a receptor on CD8+ T cells (TNF-receptor II, or TNFRII). The expression of both of these cell-surface proteins is upregulated by HIV infection or by treatment with recombinant gp120 or SDF-1. Apoptosis of CD8+ T cells isolated from HIV-infected patients is also mediated by macrophages through the interaction between mbTNF and TNFRII. These results indicate that the increased turnover of CD8+ T cells in HIV-infected subjects is mediated by the HIV envelope protein through the CXCR4 chemokine receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Surface / physiology
  • Apoptosis*
  • CD8-Positive T-Lymphocytes / pathology*
  • Cell Communication
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / physiology
  • HIV Envelope Protein gp120 / physiology*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / pathogenicity*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Macrophages / physiology*
  • Macrophages / virology
  • Receptors, CXCR4 / physiology
  • Tropism


  • Antigens, Surface
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • HIV Envelope Protein gp120
  • Receptors, CXCR4