Upregulation of fas ligand expression by human immunodeficiency virus in human macrophages mediates apoptosis of uninfected T lymphocytes

Andrew D. Badley, Julie A. McElhinny, Paul J. Leibson, David H. Lynch, Mark R. Alderson, Carlos V. Paya

Research output: Contribution to journalArticle

285 Scopus citations

Abstract

Apoptosis has been proposed to mediate CD4+ T-cell depletion in human immunodeficiency virus (HIV)-infected individuals. Interaction of Fas ligand (FasL) with Fas (CD95) results in lymphocyte apoptosis, and increased susceptibility to Fas-mediated apoptosis has been demonstrated in lymphocytes from HIV-infected individuals. Cells undergoing apoptosis in lymph nodes from HIV-infected individuals do not harbor virus, and therefore a bystander effect has been postulated to mediate apoptosis of uninfected cells. These data raise the possibility that antigen-presenting cells are a source of FasL and that HIV infection of cells such as macrophages may induce or increase FasL expression. In this report, we demonstrate that HIV infection of monocytic cells not only increases the surface expression of Fas but also results in the de novo expression of FasL. Interference with the FasL-Fas interaction by anti-Fas blocking antibodies abrogates HIV-induced apoptosis of monocytic cells. Human monocyte-derived macrophages from healthy donors contain detectable FasL mRNA, which is further upregulated following HIV infection with monocytotropic strains. HIV-infected human macrophages result in the apoptotic death of Jurkat T cells and peripheral blood T lymphocytes. Interruption of the FasL-Fas interaction abrogates the HIV-infected macrophage-dependent death of T lymphocytes. These results provide evidence that human macrophages can provide a source of FasL, especially following HIV infection, and can thus participate in lymphocyte depletion in HIV-infected individuals.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalJournal of virology
Volume70
Issue number1
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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