scholarly journals Endogenous Dendritic Cells Are Required for Amplification of T Cell Responses Induced by Dendritic Cell Vaccines In Vivo

2003 ◽  
Vol 170 (6) ◽  
pp. 2817-2823 ◽  
Author(s):  
Petra Kleindienst ◽  
Thomas Brocker
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Dendritic Cell Vaccines

scholarly journals Dysregulated NF-κB–Dependent ICOSL Expression in Human Dendritic Cell Vaccines Impairs T-cell Responses in Patients with Melanoma

2020 ◽  
Vol 8 (12) ◽  
pp. 1554-1567
Author(s):  
Deena M. Maurer ◽  
Juraj Adamik ◽  
Patricia M. Santos ◽  
Jian Shi ◽  
Michael R. Shurin ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
T Cell Responses ◽  
Human Dendritic Cell ◽  
Cell Responses ◽  
Dendritic Cell Vaccines

scholarly journals Induction of Polyomavirus-Specific CD8+T Lymphocytes by Distinct Dendritic Cell Subpopulations

2001 ◽  
Vol 75 (1) ◽  
pp. 544-547 ◽  
Author(s):  
Donald R. Drake ◽  
Mandy L. Shawver ◽  
Annette Hadley ◽  
Eric Butz ◽  
Charles Maliszewski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Epitope ◽  
T Cell Responses ◽  
T Cell Epitope ◽  
Cell Responses ◽  
Cd8 T Lymphocytes ◽  
Cell Subpopulations ◽  
Antigen Presenting

ABSTRACT Dendritic cells are pivotal antigen-presenting cells for generating adaptive T-cell responses. Here, we show that dendritic cells belonging to either the myeloid-related or lymphoid-related subset are permissive for infection by mouse polyomavirus and, when loaded with a peptide corresponding to the immunodominant anti-polyomavirus CD8+T-cell epitope or infected by polyomavirus, are each capable of driving expansion of primary polyomavirus-specific CD8+ T-cell responses in vivo.

Dendritic cells overexpressing CD95 (Fas) ligand elicit vigorous allospecific T-cell responses in vivo

Blood ◽  
2003 ◽  
Vol 101 (4) ◽  
pp. 1469-1476 ◽  
Author(s):  
Sofia Buonocore ◽  
Frédéric Paulart ◽  
Alain Le Moine ◽  
Michel Braun ◽  
Isabelle Salmon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Fas Ligand ◽  
T Cell Responses ◽  
Genetically Engineered ◽  
Peripheral Tolerance ◽  
Cytotoxic T Cell ◽  
Cell Responses

Dendritic cells (DCs) genetically engineered to overexpress CD95 (Fas) ligand (CD95L-DC) were proposed as tools to induce peripheral tolerance to alloantigens. Herein, we observed that CD95L-DC obtained after retroviral gene transfer in bone marrow (BM) precursors derived from CD95-deficient (lpr/lpr) mice elicit much stronger allospecific type 1 helper T-cell and cytotoxic T-cell activities than control DCs upon injection in vivo, although they induce lower T-cell responses in vitro. Indeed, a single injection of CD95L-DC prepared from C57BL/6 mice was sufficient to prime bm13 recipients for acute rejection of C57BL/6 skin allografts that were otherwise tolerated in the context of this single weak major histocompatibility complex (MHC) class I incompatibility. Massive neutrophil infiltrates depending on interleukin (IL)–1 signaling were observed at sites of CD95L-DC injection. Experiments in IL-1 receptor–deficient mice or in animals injected with depleting anti-Gr1 monoclonal antibody (mAb) established that neutrophil recruitment is required for the development of vigorous T-cell responses after injection of CD95L-DC in vivo.

scholarly journals Deciphering the Mechanisms of Improved Immunogenicity of Hypochlorous Acid-Treated Antigens in Anti-Cancer Dendritic Cell-Based Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 271
Author(s):  
Michele Graciotti ◽  
Fabio Marino ◽  
HuiSong Pak ◽  
Petra Baumgaertner ◽  
Anne-Christine Thierry ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Hypochlorous Acid ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Tumor Lysate ◽  
Cell Responses ◽  
Significant Difference

Hypochlorous acid (HOCl)-treated whole tumor cell lysates (Ox-L) have been shown to be more immunogenic when used as an antigen source for therapeutic dendritic cell (DC)-based vaccines, improving downstream immune responses both in vitro and in vivo. However, the mechanisms behind the improved immunogenicity are still elusive. To address this question, we conducted a proteomic and immunopeptidomics analyses to map modifications and alterations introduced by HOCl treatment using a human melanoma cell line as a model system. First, we show that one-hour HOCl incubation readily induces extensive protein oxidation, mitochondrial biogenesis, and increased expression of chaperones and antioxidant proteins, all features indicative of an activation of oxidative stress-response pathways. Characterization of the DC proteome after loading with HOCl treated tumor lysate (Ox-L) showed no significant difference compared to loading with untreated whole tumor lysate (FT-L). On the other hand, detailed immunopeptidomic analyses on monocyte-derived DCs (mo-DCs) revealed a great increase in human leukocyte antigen class II (HLA-II) presentation in mo-DCs loaded with Ox-L compared to the FT-L control. Further, 2026 HLA-II ligands uniquely presented on Ox-L-loaded mo-DCs were identified. In comparison, identities and intensities of HLA class I (HLA-I) ligands were overall comparable. We found that HLA-II ligands uniquely presented by DCs loaded with Ox-L were more solvent exposed in the structures of their source proteins, contrary to what has been hypothesized so far. Analyses from a phase I clinical trial showed that vaccinating patients using autologous Ox-L as an antigen source efficiently induces polyfunctional vaccine-specific CD4+ T cell responses. Hence, these results suggest that the increased immunogenicity of Ox-L is, at least in part, due to qualitative and quantitative changes in the HLA-II ligandome, potentially leading to an increased HLA-II dependent stimulation of the T cell compartment (i.e., CD4+ T cell responses). These results further contribute to the development of more effective and immunogenic DC-based vaccines and to the molecular understanding of the mechanism behind HOCl adjuvant properties.

scholarly journals Glycan-Modified Melanoma-Derived Apoptotic Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1266 ◽  
Author(s):  
Horrevorts ◽  
Stolk ◽  
Ven ◽  
Hulst ◽  
Hof ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Extracellular Vesicles ◽  
T Cell Responses ◽  
Intercellular Adhesion Molecule ◽  
Antigen Delivery ◽  
Vaccine Strategy ◽  
Cell Responses ◽  
High Mannose

Tumors that lack T cell infiltration are less likely to respond to immune checkpoint inhibition and could benefit from cancer vaccination for the initiation of anti-tumor T cell responses. An attractive vaccine strategy is in vivo targeting of dendritic cells (DCs), key initiators of antigen-specific T cell responses. In this study we generated tumor-derived apoptotic extracellular vesicles (ApoEVs), which are potentially an abundant source of tumor-specific neo-antigens and other tumor-associated antigens (TAAs), and which can be manipulated to express DC-targeting ligands for efficient antigen delivery. Our data demonstrates that by specifically modifying the glycocalyx of tumor cells, high-mannose glycans can be expressed on their cell surface and on extracellular vesicles derived after the induction of apoptosis. High-mannose glycans are the natural ligands of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a dendritic cell associated C-type lectin receptor (CLR), which has the ability to efficiently internalize its cargo and direct it to both major histocompatibility complex (MHC)-I and MHC-II pathways for the induction of CD8+ and CD4+ T cell responses, respectively. Compared to unmodified ApoEVs, ApoEVs carrying DC-SIGN ligands are internalized to a higher extent, resulting in enhanced priming of tumor-specific CD8+ T cells. This approach thus presents a promising vaccination strategy in support of T cell-based immunotherapy of cancer.

scholarly journals Plasmacytoid dendritic cells efficiently cross-prime naive T cells in vivo after TLR activation

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3713-3722 ◽  
Author(s):  
Juliette Mouriès ◽  
Gabriel Moron ◽  
Géraldine Schlecht ◽  
Nicolas Escriou ◽  
Gilles Dadaglio ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Antigen Processing ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cross Presentation ◽  
Cell Responses

Abstract Cross-presentation is a crucial mechanism in tumoral and microbial immunity because it allows internalized cell associated or exogenous antigens (Ags) to be delivered into the major histocompatibility complex I pathway. This pathway is important for the development of CD8+ T-cell responses and for the induction of tolerance. In mice, cross-presentation is considered to be a unique property of CD8α+ conventional dendritic cells (DCs). Here we show that splenic plasmacytoid DCs (pDCs) efficiently capture exogenous Ags in vivo but are not able to cross-present these Ags at steady state. However, in vitro and in vivo stimulation by Toll-like receptor-7, or -9 or viruses licenses pDCs to cross-present soluble or particulate Ags by a transporter associated with antigen processing-dependent mechanism. Induction of cross-presentation confers to pDCs the ability to generate efficient effector CD8+ T-cell responses against exogenous Ags in vivo, showing that pDCs may play a crucial role in induction of adaptive immune responses against pathogens that do not infect tissues of hemopoietic origin. This study provides the first evidence for an in vivo role of splenic pDCs in Ag cross-presentation and T-cell cross-priming and suggests that pDCs may constitute an attractive target to boost the efficacy of vaccines based on cytotoxic T lymphocyte induction.

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