The expression of Fas ligand by macrophages and its upregulation by human immunodeficiency virus

David H. Dockrell, Andrew D. Badley, Jorge S. Villacian, Carrie J. Heppelmann, Alicia Algeciras, Steven Ziesmer, Hideo Yagita, David H. Lynch, Patrick C. Roche, Paul J. Leibson, Carlos V. Paya

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101 Scopus citations

Abstract

Fas/Fas Ligand (FasL) interactions play a significant role in peripheral T lymphocyte homeostasis and in certain pathological states characterized by T cell depletion. In this study, we demonstrate that antigen-presenting cells such as monocyte-derived human macrophages (MDM) but not monocyte-derived dendritic cells express basal levels of FasL. HIV infection of MDM increases FasL protein expression independent of posttranslational mechanisms, thus highlighting the virus-induced transcriptional upregulation of FasL. The in vitro relevance of these observations is confirmed in human lymphoid tissue. FasL protein expression is constitutive and restricted to tissue macrophages and not dendritic cells. Moreover, a significant increase in macrophage- associated FasL is observed in lymphoid tissue from HIV (+) individuals (P < 0.001), which is further supported by increased levels of FasL mRNA using in situ hybridization. The degree of FasL protein expression in vivo correlates with the degree of tissue apoptosis (r = 0.761, P < 0.001), which is significantly increased in tissue from HIV-infected patients (P < 0.001). These results identify human tissue macrophages as a relevant source for FasL expression in vitro and in vivo and highlight the potential role of FasL expression in the immunopathogenesis of HIV infection.

Original languageEnglish (US)
Pages (from-to)2394-2405
Number of pages12
JournalJournal of Clinical Investigation
Volume101
Issue number11
DOIs
StatePublished - Jun 1 1998

Keywords

  • HIV-induced upregulation of FasL in macrophages

ASJC Scopus subject areas

  • Medicine(all)

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    Dockrell, D. H., Badley, A. D., Villacian, J. S., Heppelmann, C. J., Algeciras, A., Ziesmer, S., Yagita, H., Lynch, D. H., Roche, P. C., Leibson, P. J., & Paya, C. V. (1998). The expression of Fas ligand by macrophages and its upregulation by human immunodeficiency virus. Journal of Clinical Investigation, 101(11), 2394-2405. https://doi.org/10.1172/JCI1171