Dendritic Cell Maturation and Subsequent Enhanced T-Cell Stimulation Induced with the Novel Synthetic Immune Response Modifier R-848

• Published in: Cellular immunology 1999-10, Vol.197 (1), p.62-72
• Main Authors: Ahonen, Cory L., Gibson, Sheila J., Smith, Rose M., Pederson, Linda K., Lindh, Jana M., Tomai, Mark A., Vasilakos, John P.
• Format: Article
• Language: English
• Subjects: Antigens, CD - biosynthesis; Antigens, Surface - biosynthesis; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Division - drug effects; Cells, Cultured; Chemokines - biosynthesis; Chemokines - secretion; Cytokines - biosynthesis; Cytokines - secretion; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Imidazoles - pharmacology; Lipopolysaccharides - pharmacology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Monocytes - cytology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - secretion
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1999.1555

Agents that enhance dendritic cell maturation can enhance T-cell activation and therefore may improve the efficiency of vaccines or improve cellular immunotherapy. Previously, we demonstrated that a novel low-molecular-weight synthetic immune response modifier, R-848, induces IL-12 and IFN-α secretion from monocytes and macrophages. Here we report that R-848 induces the maturation of human monocyte-derived dendritic cells. Characteristic of dendritic cell maturation, R-848 treatment induces cell surface expression of CD83 and increases cell surface expression of CD80, CD86, CD40, and HLA-DR. Additionally, R-848 induces cytokine (IL-6, IL-12, TNF-α, IFN-α) and chemokine (IL-8, MIP-1α, MCP-1) secretion from dendritic cells. Most significantly, R-848 enhances dendritic cell antigen presenting function, as measured by increased T-cell proliferation and T-cell cytokine secretion in both allogeneic and autologous T-cell systems. Consequently, low-molecular-weight synthetic molecules such as R-848 and its derivatives may be useful as vaccine adjuvants or as ex vivo stimulators of dendritic cells for cellular immunotherapy.