Antigen Delivery to Plasmacytoid Dendritic Cells via BST2 Induces Protective T Cell-Mediated Immunity
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- Jakob Loschko
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München , D-81675 München ,
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- Andreas Schlitzer
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München , D-81675 München ,
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- Diana Dudziak
- Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Friedrich-Alexander-Universität Erlangen-Nürnberg , D-91054 Erlangen ,
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- Ingo Drexler
- Klinische Kooperationsgruppe “Antigen-spezifische Immuntherapie”, Helmholtz Zentrum München , D-81675 München ,
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- Nadja Sandholzer
- Abteilung für Klinische Pharmakologie, Klinikum der Universität München , D-80336 München ,
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- Carole Bourquin
- Abteilung für Klinische Pharmakologie, Klinikum der Universität München , D-80336 München ,
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- Wolfgang Reindl
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München , D-81675 München ,
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- Anne B Krug
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München , D-81675 München ,
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説明
<jats:title>Abstract</jats:title> <jats:p>Plasmacytoid dendritic cells (PDCs) are capable of presenting Ags to T cells in a tolerogenic or immunogenic manner depending on the formulation of the Ag and the mode of stimulation. It has not been investigated whether effective adaptive immune responses useful for vaccination can be induced by Ab-mediated Ag targeting to PDCs in vivo. In this study, we show that Ag delivered to murine PDCs via bone marrow stromal cell Ag 2 (BST2)/CD317 in combination with TLR agonists as adjuvants is specifically presented by PDCs in vivo and elicits strong cellular and humoral immune responses. These include IFN-γ production by CD4+ T cells and high Ab titers with a broad range of IgG isotypes. In addition, BST2-mediated Ag delivery in the presence of polyinosinic-polycytidylic acid as adjuvant induces cytotoxic T lymphocytes that are functional in vivo. A single immunization with Ag-fused anti-BST2 Ab together with polyinosinic-polycytidylic acid as adjuvant is sufficient to trigger protective immunity against subsequent viral infection and tumor growth. We conclude that despite the potential tolerogenic properties of PDCs, Ag targeting to PDCs in combination with TLR agonists as adjuvants is an effective vaccination strategy.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 186 (12), 6718-6725, 2011-06
Oxford University Press (OUP)