Generation of Th1-Polarizing Dendritic Cells Using the TLR7/8 Agonist CL075
| Autor: | Susanne Wilde, Barbara Mosetter, Dolores J. Schendel, Christiane Geiger, Maja Bürdek, Miran Javorovic, Bernhard Frankenberger, Stefani Spranger, Stefanie Tippmer, Iris Bigalke |
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| Rok vydání: | 2010 |
| Předmět: |
Agonist
medicine.drug_class medicine.medical_treatment Immunology C-C chemokine receptor type 7 Biology Ligands Lymphocyte Activation Cancer Vaccines Immunotherapy Adoptive Interferon-gamma Adjuvants Immunologic Cell Movement medicine Humans Immunology and Allergy Cytotoxic T cell Cells Cultured Imidazoles Cell Polarity Cell Differentiation hemic and immune systems Chemotaxis Dendritic Cells Immunotherapy TLR7 Th1 Cells Coculture Techniques Toll-Like Receptor 3 Cell biology Killer Cells Natural Thiazoles Poly I-C Toll-Like Receptor 7 Biochemistry Toll-Like Receptor 8 Quinolines Cytokines Cytokine secretion CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 185:738-747 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1000060 |
| Popis: | In this paper, we describe a new method for preparation of human dendritic cells (DCs) that secrete bioactive IL-12(p70) using synthetic immunostimulatory compounds as TLR7/8 agonists. Monocyte-derived DCs were generated using a procedure that provided mature cells within 3 d. Several maturation mixtures that contained various cytokines, IFN-γ, different TLR agonists, and PGE2 were compared for impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation. Mixtures that included the TLR7/8 agonists R848 or CL075, combined with the TLR3 agonist polyinosinic:polycytidylic acid, yielded 3-d mature DCs that secreted high levels of IL-12(p70), showed strong chemotaxis to CCR7 ligands, and had a positive costimulatory potential. They also had excellent capacity to activate NK cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and to induce T cell-mediated cytotoxic function. Thereby, mature DCs prepared within 3 d using such maturation mixtures displayed optimal functions required for vaccine development. |
| Databáze: | OpenAIRE |
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