Acquired T-cell sensitivity to TRAIL mediated killing during HIV infection is regulated by CXCR4-gp120 interactions

Julian J. Lum, David J. Schnepple, Andrew D. Badley

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: Sensitivity towards apoptosis induced by ligation of the tumor necrosis factor family of death receptors is controlled in part by death receptor expression. Whereas cellular activation enhances Fas receptor expression and induces Fas sensitivity, such cellular activation neither alters TRAIL receptor expression nor induces TRAIL sensitivity. Cells infected by HIV acquire sensitivity to TRAIL induced death, although the mechanisms by which this is achieved are undefined. Objective: To define the mechanism by which cells from HIV infected patients acquire sensitivity to TRAIL mediated killing. Design: In vitro assessment of TRAIL receptor expression and TRAIL sensitivity. Methods: Treatment of Jurkat T cells, peripheral blood lymphocytes from HIV negative donors, or human osteogenic seroma (HOS) cells expressing CD4, CXCR4 or CCR5 with T tropic gp120, M tropic gp120, or agonistic antibodies against CD4, CXCR4 or CCR5. TRAIL receptors were measured by flow cytometry or reverse transcription-PCR and TRAIL sensitivity was assessed by incubation with recombinant TRAIL followed by Annexin V fluorescein isothiocyanate/Propidium Iodide (PI) staining. Results: Treatment of uninfected Jurkat T cells, as well as primary T cells with gp120 results in the upregulation of TRAIL death receptor expression and acquired sensitivity to TRAIL mediated cell death. The increase in TRAIL death receptor expression and acquisition of TRAIL sensitivity requires the chemokine coreceptor CXCR4 but not CCR5 or the CD4 receptor. Conclusions: These results indicate that chemokine receptor interactions regulate TRAIL receptor expression and provide an explanation for the acquired T cell sensitivity to TRAIL mediated killing death during HIV infection.

Original languageEnglish (US)
Pages (from-to)1125-1133
Number of pages9
JournalAIDS
Volume19
Issue number11
DOIs
StatePublished - Jul 22 2005

Keywords

  • Apoptosis
  • CXCR4
  • HIV
  • Trail
  • gp120

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Acquired T-cell sensitivity to TRAIL mediated killing during HIV infection is regulated by CXCR4-gp120 interactions'. Together they form a unique fingerprint.

  • Cite this