Synchronization of Dendritic Cell Activation and Antigen Exposure Is Required for the Induction of Th1/Th17 Responses
| العنوان: | Synchronization of Dendritic Cell Activation and Antigen Exposure Is Required for the Induction of Th1/Th17 Responses |
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| المؤلفون: | Arun T. Kamath, Béatris Mastelic, Paul-Henri Lambert, Else Marie Agger, Peter Andersen, Claire-Anne Siegrist, Dennis Christensen, Daniel D. Pinschewer, Anne-Françoise Rochat |
| المصدر: | The Journal of Immunology The Journal of Immunology; Vol 188 Journal of Immunology, Vol. 188, No 10 (2012) pp. 4828-37 |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Lymph Nodes/immunology/pathology, Adoptive cell transfer, Recombinant Fusion Proteins, medicine.medical_treatment, Immunology, Population, Dose-Response Relationship, Immunologic, Epitopes, T-Lymphocyte, Mice, Transgenic, ddc:616.07, Lymphocyte Activation/immunology, Lymphocyte Activation, Epitope, Dendritic Cells/immunology/metabolism, Mice, 03 medical and health sciences, 0302 clinical medicine, Adjuvants, Immunologic, Antigen, In vivo, Adjuvanticity, Adjuvants, Immunologic/administration & dosage, medicine, Th17 Cells/immunology, Animals, Immunology and Allergy, Th1 Cells/immunology, Tuberculosis Vaccines, education, Cells, Cultured, Epitopes, T-Lymphocyte/administration & dosage/immunology, 030304 developmental biology, 0303 health sciences, education.field_of_study, Chemistry, Dendritic Cells, Dendritic cell, Th1 Cells, Adoptive Transfer, Cell biology, Mice, Inbred C57BL, Recombinant Fusion Proteins/administration & dosage/immunology, Th17 Cells, Tuberculosis Vaccines/administration & dosage/immunology, Female, Lymph Nodes, Adjuvant, 030215 immunology |
| الوصف: | The dendritic cell (DC) targeting/activation patterns required to elicit Th1/Th17 responses remain undefined. One postulated requirement was that of a physical linkage between Ags and immunomodulators. Accordingly, the separate same-site administration of Ag85B–ESAT-6 (hybrid-1 protein; H1), a mycobacterial fusion Ag, and the CAF01 liposome-based adjuvant induced similar Ab and weak Th2 responses as those of coformulated H1/CAF01 but failed to elicit Th1/Th17 responses. Yet, this separate same-site injection generated the same type and number of activated Ag+/adjuvant+ DCs in the draining lymph nodes (LN) as that of protective H1/CAF01 immunization. Thus, targeting/activating the same DC population by Ag and adjuvant is not sufficient to elicit Th1/Th17 responses. To identify the determinants of Th1/Th17 adjuvanticity, in vivo tracking experiments using fluorescently labeled Ag and adjuvant identified that a separate same-site administration elicits an additional early Ag+/adjuvant− DC population with a nonactivated phenotype, resulting from the earlier targeting of LN DCs by H1 than by CAF01 molecules. This asynchronous targeting pattern was mimicked by the injection of free H1 prior to or with, but not after, H1/CAF01 or H1/CpG/ aluminum hydroxide immunization. The injection of soluble OVA similarly prevented the induction of Th1 responses by OVA/CAF01. Using adoptively transferred OT-2 cells, we show that the Ag targeting of LN DCs prior to their activation generates nonactivated Ag-pulsed DCs that recruit Ag-specific T cells, trigger their initial proliferation, but interfere with Th1 induction in a dose-dependent manner. Thus, the synchronization of DC targeting and activation is a critical determinant for Th1/Th17 adjuvanticity. |
| اللغة: | English |
| تدمد: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1103183 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a80a4a487e9dded8e8c992230eae5f38 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a80a4a487e9dded8e8c992230eae5f38 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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| DOI: | 10.4049/jimmunol.1103183 |