Inability of Plasmacytoid Dendritic Cells To Directly Lyse HIV-Infected Autologous CD4 + T Cells despite Induction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand
- 15 March 2010
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 84 (6), 2762-2773
- https://doi.org/10.1128/jvi.01350-09
Abstract
The function of plasmacytoid dendritic cells (PDC) in chronic human immunodeficiency virus type 1 (HIV-1) infection remains controversial with regard to its potential for sustained alpha interferon (IFN-α) production and induction of PDC-dependent tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cytotoxicity of HIV-infected cells. We address these areas by a study of chronically HIV-1-infected subjects followed through antiretroviral therapy (ART) interruption and by testing PDC cytolytic function against autologous HIV-infected CD4 + T cells. Rebound in viremia induced by therapy interruption showed a positive association between TRAIL and viral load or T-cell activation, but comparable levels of plasma IFN-α/β were found in viremic ART-treated and control subjects. While PDC from HIV-infected subjects expressed less interferon regulator factor 7 (IRF-7) and produced significantly less IFN-α upon Toll-like receptor 7/9 (TLR7/9) engagement than controls, membrane TRAIL expression in PDC from HIV + subjects was increased. Moreover, no significant increase in death receptor 5 (DR5) expression was seen in CD4 + T cells from viremic HIV + subjects compared to controls or following in vitro infection/exposure to infectious and noninfectious virus or exogenous IFN-α, respectively. Although activated PDC killed the DR5-expressing HIV-infected Sup-T1 cell line, PDC did not lyse primary autologous HIV + CD4 + T cells yet could provide accessory help for NK cells in killing HIV-infected autologous CD4 + T cells. Taken together, our data show a lack of sustained high levels of soluble IFN-α in chronic HIV-1 infection in vivo and document a lack of direct PDC cytolytic activity against autologous infected or uninfected CD4 + T cells.Keywords
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