scholarly journals Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.

10.3791/51207 ◽  
2015 ◽  
Author(s):  
Mariana G. Bego ◽  
Édouard A. Côté ◽  
Éric A. Cohen
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Culture System ◽  
Ex Vivo ◽  
Plasmacytoid Dendritic Cells ◽  
Hiv 1

scholarly journals Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte response in vitro

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1327-1333 ◽  
Author(s):  
Andreas Gruber ◽  
June Kan-Mitchell ◽  
Kelli L. Kuhen ◽  
Tetsu Mukai ◽  
Flossie Wong-Staal
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Ex Vivo ◽  
T Cell Response ◽  
Adoptive T Cell Therapy ◽  
Cytotoxic T Cell ◽  
T Cell Therapy ◽  
Hiv 1

Abstract Dendritic cells (DCs) genetically modified to continually express and present antigens may be potent physiologic adjuvants for induction of prophylactic or therapeutic immunity. We have previously shown that an env and nef deleted HIV-1 vector (HIV-1ΔEN) pseudotyped with VSV-G transduced monocyte-derived macrophages as well as CD34+ precursors of DCs. Here we extended these findings with HIV-1ΔEN to highly differentiated human DCs derived in culture from circulating monocytes (DCs). In addition, a new vector derived from HIV-1ΔEN but further deleted in its remaining accessory genes vif, vpr, and vpu(HIV-1ΔEN V3) was also tested. Both vectors efficiently transduced DCs. Transduction of DCs did not significantly alter their viability or their immunophenotype when compared with untransduced DCs. Furthermore, the phagocytic potential of immature DCs, as well as their ability to differentiate into mature DCs capable of stimulating T-cell proliferation, was not affected. Finally, DCs transduced by the HIV-1ΔEN vector were able to elicit a primary antiviral cytotoxic T-cell response in autologous CD8 T cells. These results suggest that HIV-1–based vectors expressing viral antigens may be useful for in vivo active immunization as well as ex vivo priming of cytotoxic T cells for adoptive T-cell therapy.

scholarly journals Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte response in vitro

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1327-1333 ◽  
Author(s):  
Andreas Gruber ◽  
June Kan-Mitchell ◽  
Kelli L. Kuhen ◽  
Tetsu Mukai ◽  
Flossie Wong-Staal
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Ex Vivo ◽  
T Cell Response ◽  
Adoptive T Cell Therapy ◽  
Cytotoxic T Cell ◽  
T Cell Therapy ◽  
Hiv 1

Dendritic cells (DCs) genetically modified to continually express and present antigens may be potent physiologic adjuvants for induction of prophylactic or therapeutic immunity. We have previously shown that an env and nef deleted HIV-1 vector (HIV-1ΔEN) pseudotyped with VSV-G transduced monocyte-derived macrophages as well as CD34+ precursors of DCs. Here we extended these findings with HIV-1ΔEN to highly differentiated human DCs derived in culture from circulating monocytes (DCs). In addition, a new vector derived from HIV-1ΔEN but further deleted in its remaining accessory genes vif, vpr, and vpu(HIV-1ΔEN V3) was also tested. Both vectors efficiently transduced DCs. Transduction of DCs did not significantly alter their viability or their immunophenotype when compared with untransduced DCs. Furthermore, the phagocytic potential of immature DCs, as well as their ability to differentiate into mature DCs capable of stimulating T-cell proliferation, was not affected. Finally, DCs transduced by the HIV-1ΔEN vector were able to elicit a primary antiviral cytotoxic T-cell response in autologous CD8 T cells. These results suggest that HIV-1–based vectors expressing viral antigens may be useful for in vivo active immunization as well as ex vivo priming of cytotoxic T cells for adoptive T-cell therapy.

scholarly journals NK Cell Lysis of HIV-1-Infected Autologous CD4 Primary T Cells: Requirement for IFN-Mediated NK Activation by Plasmacytoid Dendritic Cells

2007 ◽  
Vol 179 (4) ◽  
pp. 2097-2104 ◽  
Author(s):  
Costin Tomescu ◽  
Jihed Chehimi ◽  
Vernon C. Maino ◽  
Luis J. Montaner
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Nk Cell ◽  
Cell Lysis ◽  
Plasmacytoid Dendritic Cells ◽  
Hiv 1

Tolerogenic dendritic cells modulate pathogenic CD4+ T cells in an ex vivo co-culture system in a concanavalin A-mice model of type-I autoimmune hepatitis

2020 ◽  
Vol 73 ◽  
pp. S298-S299
Author(s):  
Ranjana W. Minz ◽  
Prabhsimran Singh ◽  
Lekha Rani ◽  
Mohan Ramachandra Wani ◽  
Yashwant Kumar ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Autoimmune Hepatitis ◽  
Concanavalin A ◽  
Cd4 T Cells ◽  
Culture System ◽  
Ex Vivo ◽  
Type I ◽  
Mice Model ◽  
Tolerogenic Dendritic Cells

scholarly journals Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells

2005 ◽  
Vol 102 (39) ◽  
pp. 13974-13979 ◽  
Author(s):  
J.-P. Herbeuval ◽  
A. W. Hardy ◽  
A. Boasso ◽  
S. A. Anderson ◽  
M. J. Dolan ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Type I Ifn ◽  
Hiv 1

scholarly journals Inability of Plasmacytoid Dendritic Cells To Directly Lyse HIV-Infected Autologous CD4+ T Cells despite Induction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

2009 ◽  
Vol 84 (6) ◽  
pp. 2762-2773 ◽  
Author(s):  
Jihed Chehimi ◽  
Emmanouil Papasavvas ◽  
Costin Tomescu ◽  
Bethsebah Gekonge ◽  
Shaheed Abdulhaqq ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
T Cell Activation ◽  
Tumor Necrosis ◽  
Cell Activation ◽  
Plasmacytoid Dendritic Cells ◽  
Death Receptor 5 ◽  
Hiv 1 ◽  
Necrosis Factor

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.

Plasmacytoid dendritic cells express TRAIL and induce CD4+ T-cell apoptosis in HIV-1 viremic patients

Blood ◽  
2009 ◽  
Vol 114 (18) ◽  
pp. 3854-3863 ◽  
Author(s):  
Georg Stary ◽  
Irene Klein ◽  
Sabine Kohlhofer ◽  
Frieder Koszik ◽  
Thomas Scherzer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Trail Expression ◽  
Viral Loads ◽  
T Cell Apoptosis ◽  
Definition Of ◽  
Hiv 1 ◽  
Necrosis Factor

AbstractArtificial Toll-like receptor 7/8 (TLR7/8) ligands can endow plasmacytoid dendritic cells (pDCs) with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–dependent lytic properties. Keeping in mind that ssRNA serves as natural TLR7/8 ligand, we searched for TRAIL-expressing cells in persons infected with HIV and identified TRAIL+ pDCs in HIV-1 viremic persons, but not in nonviremic and healthy persons. TRAIL expression on pDCs was directly correlated with individual viral loads. Conversely, HIV-1 viremia was found to be associated with the up-regulation of the apoptosis-transmitting receptor TRAIL R1 on activated CD4+ T cells. As a consequence, the latter became susceptible to TRAIL-dependent pDC-mediated killing. In contrast, initiation of antiretroviral therapy led to the up-regulation of apoptosis-inhibiting TRAIL R4 on CD4+ T cells, which subsequently became resistant against pDC-mediated cellular injury. Definition of pDCs as killers of CD4+ T cells implies a new mechanism of disease progression in HIV infection.

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