title: TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells.
abstract: There is now considerable in vitro evidence that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is involved in HIV-1 pathogenesis by inducing CD4+ T-cell death characteristic of AIDS. Therefore, we have tested levels of TRAIL in plasma samples from 107 HIV-1-infected and 53 uninfected controls as well as in longitudinal plasma samples from patients who started antiretroviral therapy (ART). TRAIL was elevated in plasma of HIV-1-infected patients compared with uninfected individuals, and patients receiving ART showed decreased plasma TRAIL levels that correlated with reduction in viral load. In vitro exposure to infectious and noninfectious HIV-1 induced TRAIL in monocytes and marginally in dendritic cells (DCs) but not in macrophages or T cells. Interestingly, the HIV-1 entry inhibitor, soluble CD4, blocked HIV-1-induced production of TRAIL. Furthermore, production and gene expression of TRAIL by monocytes were regulated by type I interferon via signal transducer and activator of transcription-1 (STAT1)/STAT2 signaling molecule. Ex vivo HIV-1 infection of human tonsil lymphoid tissue also resulted in increased TRAIL production. We demonstrate here that plasma TRAIL is elevated in HIV-1-infected patients and is decreased by ART therapy. The high production of TRAIL by antigen-presenting cells may contribute to the death of CD4+ T cells during progression to AIDS.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), 9000 Rockville Pike, Bethesda, MD, USA.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Herbeuval
authors.forename: Adriano
authors.initials: A
authors.lastname: Boasso
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Grivel
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Hardy
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Anderson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dolan
authors.forename: Claire
authors.initials: C
authors.lastname: Chougnet
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Gene M
authors.initials: GM
authors.lastname: Shearer
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D050794:STAT1 Transcription Factor / Q000276:immunology / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*; D019562:Viral Load
chemical_list: D051017:Apoptosis Regulatory Proteins; D015704:CD4 Antigens; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha