1. Generation of Th1-Polarizing Dendritic Cells Using the TLR7/8 Agonist CL075
- Author
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Susanne Wilde, Barbara Mosetter, Dolores J. Schendel, Christiane Geiger, Maja Bürdek, Miran Javorovic, Bernhard Frankenberger, Stefani Spranger, Stefanie Tippmer, and Iris Bigalke
- Subjects
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 - Abstract
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.
- Published
- 2010