Costimulatory pathways mediate monocyte-dependent lymphocyte apoptosis in HIV

Dorothy E. Lewis, Derek S. Ng Tang, Xiaoping Wang, Claudia Kozinetz

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Examination of annexin V binding, an indicator of early apoptosis, on lymphocytes from HIV+ people immediately after isolation showed that both CD4+ and CD8+ T cells were apoptotic, whereas B cell apoptosis was induced mainly after incubation. CD8+ T cell apoptosis correlated with fewer CD4+ T cells, but not the level of viremia. To determine potential mechanisms for apoptosis, we examined FasL expression, which was dramatically elevated on CD14+ monocytes; however, antibody to FasL did not reproducibly inhibit apoptosis. Rather, CD8+ T cell apoptosis was caused by antigen-presenting cells because removal of monocytes or addition of antibodies to CD80 and CD86 reduced apoptosis. B cell apoptosis also involved costimulatory signals delivered by T cells but not monocytes. A unique CD8(bright)CD28(dim) T cell population died after costimulation by monocytes. Because this population was increased in patients with undetectable viremia, abnormal antigen-presenting cells may contribute to continued CD8+ T cell exhaustion by inducing apoptosis.

Original languageEnglish (US)
Pages (from-to)302-312
Number of pages11
JournalClinical Immunology
Volume90
Issue number3
DOIs
StatePublished - Jan 1 1999

Keywords

  • Annexin V
  • Apoptosis
  • Fas
  • Fas-ligand
  • HIV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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