title: Role of heterogeneous cell population on modulation of dendritic cell phenotype and activation of CD8 T cells for use in cell-based immunotherapies.
abstract: Dendritic cell (DC)-based immunotherapies have much utility in their ability to prime antigen-specific adaptive immune responses. However, there does not yet exist a consensus standard to how DCs should be primed. In this study, we aimed to determine the role of heterogeneous co-cultures, composed of both CD11c+ (DCs) and CD11c- cells, in combination with monophosphoryl lipid A (MPLA) stimulation on DC phenotype and function. Upon DC priming in different co-culture ratios, we observed reduced expression of MHCII and CD86 and increased antigen uptake among CD11c+ cells in a CD11c- dependent manner. DCs from all culture conditions were induced to mature by MPLA treatment, as determined by secretion of pro-inflammatory cytokines IL-12 and TNF-α. Antigen-specific stimulation of CD4+ T cells was not modulated by co-culture composition, in terms of proliferation nor levels of IFN-γ. However, the presence of CD11c- cells enhanced cross-presentation to CD8+ T cells compared to purified CD11c+ cells, resulting in increased cell proliferation along with higher IFN-γ production. These findings demonstrate the impact of cell populations present during DC priming, and point to the use of heterogeneous cultures of DCs and innate immune cells to enhance cell-mediated immunity.
authors: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA 98105, USA.
authors: Hannah
authors: H
authors: Frizzell
authors: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA 98105, USA.
authors: Jaehyung
authors: J
authors: Park
authors: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA 98105, USA.
authors: Natacha
authors: N
authors: Comandante Lou
authors: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA 98105, USA. Electronic address: woodrow@uw.edu.
authors: Kim A
authors: KA
authors: Woodrow
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; C048436:monophosphoryl lipid A
keywords: Bone marrow; Cell activation; Dendritic cells; Immunotherapy; Priming protocol; T cells; Toll-like receptors (TLRs)