Inability of plasmacytoid dendritic cells to directly lyse HIV-infected autologous CD4+ T cells despite induction of tumor necrosis factor-related apoptosis-inducing ligand Article

cited authors

  • Chehimi, J; Papasavvas, E; Tomescu, C; Gekonge, B; Abdulhaqq, S; Raymond, A; Hancock, A; Vinekar, K; Carty, C; Reynolds, G; Pistilli, M; Mounzer, K; Kostman, J; Montaner, LJ

fiu authors

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. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

publication date

  • March 1, 2010

Digital Object Identifier (DOI)

start page

  • 2762

end page

  • 2773

volume

  • 84

issue

  • 6