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Wyszukujesz frazę ""Davoust, Jean"" wg kryterium: Autor


Tytuł :
IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses
Autorzy :
Evnouchidou, IriniAff1, Aff2
Chappert, PascalAff2, Aff3
Benadda, Samira
Zucchetti, Andres
Weimershaus, Mirjana
Bens, Marcelle
Caillens, Vivien
Koumantou, Despoina
Lotersztajn, Sophie
van Endert, Peter
Davoust, JeanAff3, Aff5
Guermonprez, PierreAff1, Aff6
Hivroz, Claire
Gross, David A.Aff1, Aff7
Saveanu, Loredana
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Źródło :
Nature Communications. 11(1)
Czasopismo naukowe
Tytuł :
The pro-tolerogenic environment of the liver makes this tissue an ideal target for gene replacement strategies. In other peripheral tissues such as the skeletal muscle, anti-transgene immune response can result in partial or complete clearance of the transduced fibers. Here, we characterized liver-induced transgene tolerance after simultaneous transduction of liver and muscle. A clinically relevant transgene, α-sarcoglycan, mutated in limb-girdle muscular dystrophy type 2D, was fused with the SIINFEKL epitope (hSGCA-SIIN) and expressed with adeno-associated virus vectors (AAV-hSGCA-SIIN). Intramuscular delivery of AAV-hSGCA-SIIN resulted in a strong inflammatory response, which could be prevented and reversed by concomitant liver expression of the same antigen. Regulatory T cells and upregulation of checkpoint inhibitor receptors were required to establish and maintain liver-mediated peripheral tolerance. This study identifies the fundamental role of the synergy between Tregs and upregulation of checkpoint inhibitor receptors in the liver-mediated control of anti-transgene immunity triggered by muscle-directed gene transfer.
Autorzy :
Poupiot, Jérôme
Costa Verdera, Helena
Hardet, Romain
Colella, Pasqualina
Collaud, Fanny
Bartolo, Laurent
Davoust, Jean
Sanatine, Peggy
Mingozzi, Federico
Richard, Isabelle
Ronzitti, Giuseppe
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Temat :
Cytology
gene transfer
liver
QH573-671
peripheral tolerance
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Tregs
PD-1
Article
QH426-470
Genetics
LAG3
AAV
checkpoint inhibitors
Źródło :
Molecular Therapy: Methods & Clinical Development, Vol 15, Iss, Pp 83-100 (2019)
Molecular Therapy - Methods & Clinical Development, 2019, 15, pp.83-100. ⟨10.1016/j.omtm.2019.08.012⟩
Molecular Therapy. Methods & Clinical Development
Molecular Therapy - Methods & Clinical Development
Tytuł :
Role of Regulatory T Cell and Effector T Cell Exhaustion in Liver-Mediated Transgene Tolerance in Muscle
The pro-tolerogenic environment of the liver makes this tissue an ideal target for gene replacement strategies. In other peripheral tissues such as the skeletal muscle, anti-transgene immune response can result in partial or complete clearance of the transduced fibers. Here, we characterized liver-induced transgene tolerance after simultaneous transduction of liver and muscle. A clinically relevant transgene, α-sarcoglycan, mutated in limb-girdle muscular dystrophy type 2D, was fused with the SIINFEKL epitope (hSGCA-SIIN) and expressed with adeno-associated virus vectors (AAV-hSGCA-SIIN). Intramuscular delivery of AAV-hSGCA-SIIN resulted in a strong inflammatory response, which could be prevented and reversed by concomitant liver expression of the same antigen. Regulatory T cells and upregulation of checkpoint inhibitor receptors were required to establish and maintain liver-mediated peripheral tolerance. This study identifies the fundamental role of the synergy between Tregs and upregulation of checkpoint inhibitor receptors in the liver-mediated control of anti-transgene immunity triggered by muscle-directed gene transfer.
Autorzy :
Poupiot, Jérôme
Costa Verdera, Helena
Hardet, Romain
Colella, Pasqualina
Collaud, Fanny
Bartolo, Laurent
Davoust, Jean
Sanatine, Peggy
Mingozzi, Federico
Richard, Isabelle
Ronzitti, Giuseppe
Pokaż więcej
Temat :
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Źródło :
Molecular Therapy - Methods & Clinical Development
Molecular Therapy - Methods & Clinical Development, 2019, 15, pp.83-100. ⟨10.1016/j.omtm.2019.08.012⟩
Tytuł :
Foxp3+ regulatory T cells (Tregs) play a major role in acquired immune tolerance to allogenic transplants. Their suppressive activity is thought to require T cell receptor (TCR)-driven antigen recognition; little, however, is known about the fraction of Tregs able to recognize alloantigens within this T cell subset primarily educated against self-antigens. Performing transfer experiments of Tregs or conventional T cells (Tconv) into both lymphoreplete and lymphopenic mice, we observed a similarly high proportion of cells signaling through their TCR and proliferating in allogenic hosts. Furthermore, using an in vivo proliferation assay with limited T cell numbers infused into lymphopenic mice, we found that the overall frequency of alloreactive Tregs was similar if not higher to that of alloreactive Tconv. Overall our study highlights a noticeably high level of alloreactive Foxp3+ regulatory T cells accounting for their predominant role in transplantation tolerance.
Autorzy :
Lalfer, Mélanie
Chappert, Pascal
Carpentier, Maxime
Urbain, Dominique
Davoust, Jean
Gross, David-Alexandre
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Temat :
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
ComputingMilieux_MISCELLANEOUS
Źródło :
Frontiers in Immunology, Frontiers, 2019, 10, ⟨10.3389/fimmu.2019.00521⟩
Tytuł :
Foxp3+ Regulatory and Conventional CD4+ T Cells Display Similarly High Frequencies of Alloantigen-Reactive Cells
Foxp3+ regulatory T cells (Tregs) play a major role in acquired immune tolerance to allogenic transplants. Their suppressive activity is thought to require T cell receptor (TCR)-driven antigen recognition; little, however, is known about the fraction of Tregs able to recognize alloantigens within this T cell subset primarily educated against self-antigens. Performing transfer experiments of Tregs or conventional T cells (Tconv) into both lymphoreplete and lymphopenic mice, we observed a similarly high proportion of cells signaling through their TCR and proliferating in allogenic hosts. Furthermore, using an in vivo proliferation assay with limited T cell numbers infused into lymphopenic mice, we found that the overall frequency of alloreactive Tregs was similar if not higher to that of alloreactive Tconv. Overall our study highlights a noticeably high level of alloreactive Foxp3+ regulatory T cells accounting for their predominant role in transplantation tolerance.
Autorzy :
Lalfer, Mélanie
Chappert, Pascal
Carpentier, Maxime
Urbain, Dominique
Davoust, Jean
Gross, David-Alexandre
Pokaż więcej
Temat :
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Źródło :
Frontiers in Immunology, Frontiers, 2019, 10, ⟨10.3389/fimmu.2019.00521⟩
Tytuł :
Cross-Presentation of Skin-Targeted Recombinant Adeno-associated Virus 2/1 Transgene Induces Potent Resident Memory CD8 + T Cell Responses
A key aspect to consider for vaccinal protection is the induction of a local line of defense consisting of nonrecirculating tissue-resident memory T cells (TRM), in parallel to the generation of systemic memory CD8+ T cell responses. The potential to induce TRM has now been demonstrated for a number of pathogens and viral vectors. This potential, however, has never been tested for recombinant adeno-associated virus (rAAV) vectors, which are weakly inflammatory and poor transducer of dendritic cells. Using a model rAAV2/1-based vaccine, we determined that a single intradermal immunization with rAAV2/1 vectors in mice induces fully functional TRM at the local site of immunization. The optimal differentiation of rAAV-induced transgene-specific skin TRM was dependent on local transgene expression and additional CD4+ T cell help. Transgene expression in dendritic cells, however, appeared to be dispensable for the priming of transgene-specific skin TRM, suggesting that this process solely depends on the cross-presentation of transgene products. Overall, this study provides needed information to properly assess rAAV vectors as T cell-inducing vaccine carriers.IMPORTANCE rAAVs display numerous characteristics that could make them extremely attractive as vaccine carriers, including an excellent safety profile in humans and great flexibility regarding serotypes and choice of target tissue. Studies addressing the ability of rAAV to induce protective T cell responses, however, are scarce. Notably, the potential to induce a tissue-resident memory T cell response has never been described for rAAV vectors, strongly limiting further interest for their use as vaccine carriers. Using a model rAAV2/1 vaccine delivered to the skin, our study demonstrated that rAAV vectors can induce bona fide skin resident TRM and provides additional clues regarding the cellular mechanisms underlying this process. These results will help widen the field of rAAV applications.
Autorzy :
Gross, David-Alexandre
Ghenassia, Alexandre
Bartolo, Laurent
Urbain, Dominique
Benkhelifa-Ziyyat, Sofia
Lorain, Stéphanie
Davoust, Jean
Chappert, Pascal
Pokaż więcej
Temat :
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Źródło :
Journal of Virology, American Society for Microbiology, 2019, 93 (5), ⟨10.1128/JVI.01334-18⟩
Tytuł :
A key aspect to consider for vaccinal protection is the induction of a local line of defense consisting of nonrecirculating tissue-resident memory T cells (TRM), in parallel to the generation of systemic memory CD8+ T cell responses. The potential to induce TRM has now been demonstrated for a number of pathogens and viral vectors. This potential, however, has never been tested for recombinant adeno-associated virus (rAAV) vectors, which are weakly inflammatory and poor transducer of dendritic cells. Using a model rAAV2/1-based vaccine, we determined that a single intradermal immunization with rAAV2/1 vectors in mice induces fully functional TRM at the local site of immunization. The optimal differentiation of rAAV-induced transgene-specific skin TRM was dependent on local transgene expression and additional CD4+ T cell help. Transgene expression in dendritic cells, however, appeared to be dispensable for the priming of transgene-specific skin TRM, suggesting that this process solely depends on the cross-presentation of transgene products. Overall, this study provides needed information to properly assess rAAV vectors as T cell-inducing vaccine carriers.IMPORTANCE rAAVs display numerous characteristics that could make them extremely attractive as vaccine carriers, including an excellent safety profile in humans and great flexibility regarding serotypes and choice of target tissue. Studies addressing the ability of rAAV to induce protective T cell responses, however, are scarce. Notably, the potential to induce a tissue-resident memory T cell response has never been described for rAAV vectors, strongly limiting further interest for their use as vaccine carriers. Using a model rAAV2/1 vaccine delivered to the skin, our study demonstrated that rAAV vectors can induce bona fide skin resident TRM and provides additional clues regarding the cellular mechanisms underlying this process. These results will help widen the field of rAAV applications.
Autorzy :
Gross, David-Alexandre
Ghenassia, Alexandre
Bartolo, Laurent
Urbain, Dominique
Benkhelifa-Ziyyat, Sofia
Lorain, Stéphanie
Davoust, Jean
Chappert, Pascal
Pokaż więcej
Temat :
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
ComputingMilieux_MISCELLANEOUS
Źródło :
Journal of Virology, American Society for Microbiology, 2019, 93 (5), ⟨10.1128/JVI.01334-18⟩
Tytuł :
Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment
Autorzy :
Ngo Nyekel, Flavie
Pacreau, Emeline
Benadda, Samira
Msallam, Rasha
Åbrink, Magnus
Pejler, Gunnar
Davoust, Jean
Benhamou, Marc
Charles, Nicolas
Launay, Pierre
Blank, Ulrich
Gautier, Gregory
Pokaż więcej
Temat :
degranulation
mast cells
neutrophils
skin
transplantation
[SDV.IMM]Life Sciences [q-bio]/Immunology
Źródło :
Frontiers in Immunology, Frontiers, 2018, 9, pp.2690. ⟨10.3389/fimmu.2018.02690⟩
Tytuł :
Intradermal Immunization with rAAV1 Vector Induces Robust Memory CD8+ T Cell Responses Independently of Transgene Expression in DCs
Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8+ T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8+ T cell responses. The intradermal route of immunization and the presence of potent major histocompatibility complex (MHC) class II responses showed synergistic effects on the overall quantity and quality of systemic long-term effector memory transgene-specific CD8+ T cells being generated against the transgene. Of key interest, we found that the induction of memory cytotoxic T lymphocytes (CTLs) following intradermal immunization was solely dependent on the cross-presentation of skin-expressed transgene products, which appeared highly enhanced as compared to muscle-expressed transgene products. Overall our results highlight key tissue-specific differences in transgene presentation pathway requirements of importance for the design of rAAV-based T cell-inducing vaccines.
Autorzy :
Ghenassia, Alexandre
Gross, David-Alexandre
Lorain, Stéphanie
Tros, Fabiola
Urbain, Dominique
Benkhelifa-Ziyyat, Sofia
Charbit, Alain
Davoust, Jean
Chappert, Pascal
Pokaż więcej
Temat :
[SDV]Life Sciences [q-bio]
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Źródło :
Molecular Therapy, Nature Publishing Group, 2017, 25 (10), pp.2309-2322. ⟨10.1016/j.ymthe.2017.06.019⟩
Tytuł :
Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8+ T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8+ T cell responses. The intradermal route of immunization and the presence of potent major histocompatibility complex (MHC) class II responses showed synergistic effects on the overall quantity and quality of systemic long-term effector memory transgene-specific CD8+ T cells being generated against the transgene. Of key interest, we found that the induction of memory cytotoxic T lymphocytes (CTLs) following intradermal immunization was solely dependent on the cross-presentation of skin-expressed transgene products, which appeared highly enhanced as compared to muscle-expressed transgene products. Overall our results highlight key tissue-specific differences in transgene presentation pathway requirements of importance for the design of rAAV-based T cell-inducing vaccines.
Autorzy :
Ghenassia, Alexandre
Gross, David-Alexandre
Lorain, Stéphanie
Tros, Fabiola
Urbain, Dominique
Benkhelifa-Ziyyat, Sofia
Charbit, Alain
Davoust, Jean
Chappert, Pascal
Pokaż więcej
Temat :
[SDV]Life Sciences [q-bio]
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
ComputingMilieux_MISCELLANEOUS
Źródło :
Molecular Therapy, Nature Publishing Group, 2017, 25 (10), pp.2309-2322. ⟨10.1016/j.ymthe.2017.06.019⟩
Tytuł :
Intrinsic Transgene Immunogenicity Gears CD8+ T-cell Priming After rAAV-Mediated Muscle Gene Transfer
Autorzy :
Lorain, Stéphanie
Gross, David-Alexandre
Goyenvalle, Aurélie
Danos, Olivier
Davoust, Jean
Garcia, Luis
Pokaż więcej
Temat :
[SDV]Life Sciences [q-bio]
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Źródło :
Molecular Therapy, Nature Publishing Group, 2015, 23 (4), pp.697-706. ⟨10.1038/mt.2014.235⟩

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