Inability of plasmacytoid dendritic cells to directly lyse HIV-infected autologous CD4+ T cells despite induction of tumor necrosis factor-related apoptosis-inducing ligand.
Enviado por Luis Montaner el
Título | Inability of plasmacytoid dendritic cells to directly lyse HIV-infected autologous CD4+ T cells despite induction of tumor necrosis factor-related apoptosis-inducing ligand. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Autores | 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 |
Journal | J Virol |
Volume | 84 |
Issue | 6 |
Pagination | 2762-73 |
Date Published | 2010 Mar |
ISSN | 1098-5514 |
Palabras clave | Animals, CD4-Positive T-Lymphocytes, Cell Line, Dendritic Cells, Female, HIV Infections, HIV-1, Humans, Interferon Regulatory Factor-7, Interferon-alpha, Killer Cells, Natural, Male, Receptors, TNF-Related Apoptosis-Inducing Ligand, TNF-Related Apoptosis-Inducing Ligand, Viral Load, Viremia |
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-alpha) 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-alpha/beta 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-alpha 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-alpha, 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-alpha in chronic HIV-1 infection in vivo and document a lack of direct PDC cytolytic activity against autologous infected or uninfected CD4(+) T cells. |
DOI | 10.1128/JVI.01350-09 |
Alternate Journal | J. Virol. |
PubMed ID | 20042498 |
PubMed Central ID | PMC2826047 |
Grant List | AI 0587780 / AI / NIAID NIH HHS / United States AI 068405 / AI / NIAID NIH HHS / United States AI 073219 / AI / NIAID NIH HHS / United States AI 51225 / AI / NIAID NIH HHS / United States UO1 AI065279 / AI / NIAID NIH HHS / United States |