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acDCs enhance human antigen-specific T-cell responses

Identifieur interne : 004602 ( PascalFrancis/Curation ); précédent : 004601; suivant : 004603

acDCs enhance human antigen-specific T-cell responses

Auteurs : Emanuela Martinuzzi [France] ; Georgia Afonso [France] ; Marie-Claude Gagnerault [France] ; Gaetano Naselli [France] ; Diana Mittag [Australie] ; Béhazine Combadiere [France] ; Christian Boitard [France] ; Nathalie Chaput [France] ; Laurence Zitvogel [France] ; Leonard C. Harrison [Australie] ; Roberto Mallone [France]

Source :

RBID : Pascal:11-0412241

Descripteurs français

English descriptors

Abstract

Detection of human Ag-specific T cells is limited by sensitivity and blood requirements. As dendritic cells (DCs) can potently stimulate T cells, we hypothesized that their induction in PBMCs in situ could link Ag processing and presentation to Ag-specific T-cell activation. To this end, unfractionated PBMCs (fresh or frozen) or whole blood were incubated for 48 hours with protein or peptide Ag together with different DC-activating agents to rapidly and sequentially induce, pulse, and mature DCs. DC activation was therefore lined up with Ag recognition by neighboring T cells, thus telescoping the sequential steps of T-cell activation. Efficient processing of protein Ags made prior knowledge of epitopes and HLA restrictions dispensable. While reducing stimulation time, manipulation and blood requirements, in situ DC induction specifically amplified Ag-specific T-cell responses (cytokine secretion, proliferation, CD137/CD154 up-regulation, and binding of peptide-HLA multimers). IL-1β, although released by DCs, was also secreted in an Ag-specific fashion, thus providing an indirect biomarker of T-cell responses. These accelerated cocultured DC (acDC) assays offered a sensitive means with which to evaluate T-cell responses to viral and melanoma Ag vaccination, and may therefore find application for immune monitoring in viral, tumor, autoimmune, and transplantation settings.
pA  
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A08 01  1  ENG  @1 acDCs enhance human antigen-specific T-cell responses
A11 01  1    @1 MARTINUZZI (Emanuela)
A11 02  1    @1 AFONSO (Georgia)
A11 03  1    @1 GAGNERAULT (Marie-Claude)
A11 04  1    @1 NASELLI (Gaetano)
A11 05  1    @1 MITTAG (Diana)
A11 06  1    @1 COMBADIERE (Béhazine)
A11 07  1    @1 BOITARD (Christian)
A11 08  1    @1 CHAPUT (Nathalie)
A11 09  1    @1 ZITVOGEL (Laurence)
A11 10  1    @1 HARRISON (Leonard C.)
A11 11  1    @1 MALLONE (Roberto)
A14 01      @1 Inserm U986, Diabetes & Autoimmunity Research Laboratory @2 Paris @3 FRA @Z 1 aut. @Z 2 aut. @Z 3 aut. @Z 4 aut. @Z 7 aut. @Z 11 aut.
A14 02      @1 Université Paris Descartes, Faculté de Médecine Rene Descartes @2 Paris @3 FRA @Z 1 aut. @Z 2 aut. @Z 3 aut. @Z 4 aut. @Z 7 aut. @Z 11 aut.
A14 03      @1 The Walter and Eliza Hall Institute of Medical Research, Parkville @2 Victoria @3 AUS @Z 5 aut. @Z 10 aut.
A14 04      @1 Inserm U945 @2 Paris @3 FRA @Z 6 aut.
A14 05      @1 Université Pierre et Marie Curie, Laboratory of Immunity and Infection @2 Paris @3 FRA @Z 6 aut.
A14 06      @1 Inserm U1015, Institut Gustave Roussy @2 Villejuif @3 FRA @Z 8 aut. @Z 9 aut.
A14 07      @1 Centre d'Investigation Clinique Biothérapie 507 @2 Villejuif @3 FRA @Z 8 aut. @Z 9 aut.
A14 08      @1 Université de Médecine Kremlin Bicêtre @2 Paris @3 FRA @Z 9 aut.
A20       @1 2128-2137
A21       @1 2011
A23 01      @0 ENG
A43 01      @1 INIST @2 3178 @5 354000508970090150
A44       @0 0000 @1 © 2011 INIST-CNRS. All rights reserved.
A45       @0 37 ref.
A47 01  1    @0 11-0412241
A60       @1 P
A61       @0 A
A64 01  1    @0 Blood
A66 01      @0 USA
C01 01    ENG  @0 Detection of human Ag-specific T cells is limited by sensitivity and blood requirements. As dendritic cells (DCs) can potently stimulate T cells, we hypothesized that their induction in PBMCs in situ could link Ag processing and presentation to Ag-specific T-cell activation. To this end, unfractionated PBMCs (fresh or frozen) or whole blood were incubated for 48 hours with protein or peptide Ag together with different DC-activating agents to rapidly and sequentially induce, pulse, and mature DCs. DC activation was therefore lined up with Ag recognition by neighboring T cells, thus telescoping the sequential steps of T-cell activation. Efficient processing of protein Ags made prior knowledge of epitopes and HLA restrictions dispensable. While reducing stimulation time, manipulation and blood requirements, in situ DC induction specifically amplified Ag-specific T-cell responses (cytokine secretion, proliferation, CD137/CD154 up-regulation, and binding of peptide-HLA multimers). IL-1β, although released by DCs, was also secreted in an Ag-specific fashion, thus providing an indirect biomarker of T-cell responses. These accelerated cocultured DC (acDC) assays offered a sensitive means with which to evaluate T-cell responses to viral and melanoma Ag vaccination, and may therefore find application for immune monitoring in viral, tumor, autoimmune, and transplantation settings.
C02 01  X    @0 002B19
C03 01  X  FRE  @0 Homme @5 02
C03 01  X  ENG  @0 Human @5 02
C03 01  X  SPA  @0 Hombre @5 02
C03 02  X  FRE  @0 Réponse immune @5 03
C03 02  X  ENG  @0 Immune response @5 03
C03 02  X  SPA  @0 Respuesta inmune @5 03
C03 03  X  FRE  @0 Hématologie @5 05
C03 03  X  ENG  @0 Hematology @5 05
C03 03  X  SPA  @0 Hematología @5 05
C03 04  X  FRE  @0 Spécificité antigénique @4 CD @5 96
C03 04  X  ENG  @0 Antigen specific @4 CD @5 96
N21       @1 283
N44 01      @1 OTO
N82       @1 OTO

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Pascal:11-0412241

Le document en format XML

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<div type="abstract" xml:lang="en">Detection of human Ag-specific T cells is limited by sensitivity and blood requirements. As dendritic cells (DCs) can potently stimulate T cells, we hypothesized that their induction in PBMCs in situ could link Ag processing and presentation to Ag-specific T-cell activation. To this end, unfractionated PBMCs (fresh or frozen) or whole blood were incubated for 48 hours with protein or peptide Ag together with different DC-activating agents to rapidly and sequentially induce, pulse, and mature DCs. DC activation was therefore lined up with Ag recognition by neighboring T cells, thus telescoping the sequential steps of T-cell activation. Efficient processing of protein Ags made prior knowledge of epitopes and HLA restrictions dispensable. While reducing stimulation time, manipulation and blood requirements, in situ DC induction specifically amplified Ag-specific T-cell responses (cytokine secretion, proliferation, CD137/CD154 up-regulation, and binding of peptide-HLA multimers). IL-1β, although released by DCs, was also secreted in an Ag-specific fashion, thus providing an indirect biomarker of T-cell responses. These accelerated cocultured DC (acDC) assays offered a sensitive means with which to evaluate T-cell responses to viral and melanoma Ag vaccination, and may therefore find application for immune monitoring in viral, tumor, autoimmune, and transplantation settings.</div>
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