In vivo generation of dendritic cells by intramuscular codelivery of FLT3 ligand and GM-CSF plasmids

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Abstract

Dendritic cells (DCs) are the major cells responsible for the uptake and the transport of antigens to regional lymphoid tissues and for the presentation of antigenic peptides to T cells. They are highly effective in immunotherapy. However, in lymphoid and other tissues, DCs constitute only a small population and are difficult to isolate in large numbers. Our objective was to devise a method with which to rapidly expand splenic DCs in vivo. We accomplished this by intramuscular injection of plasmids encoding mouse granulocyte-macrophage colony stimulating factor (GM-CSF) and fms-like tyrosine kinase 3-ligand (FLT3-L). Gene transfer was amplified by electroporation. Both cytokine vectors significantly increased DC numbers, but they were more effective in combination. When either control plasmid (Blank), or FLT3-L or GM-CSF expression plasmids were injected individually, the mean numbers of CD11c+/MHC II+ DCs in spleen cell suspensions were, respectively, 6, 11, and 23 million. When FLT3-L and GM-CSF plasmids were codelivered, this increased to 36 million. Peak levels occurred 7 days postinjection of DNA. To further characterize these DCs, we stained them with myeloid (CD11b, F4/80)- and lymphoid (CD8α)-related markers. FLT3-L cDNA favored lymphoid DC expansion and GM-CSF cDNA favored myeloid DC expansion, whereas combined treatment expanded both types with a myeloid predominance. We confirm the ability of these DCs to present antigen to CD4+ T cells and to stimulate in mixed lymphocyte cultures. We demonstrate that DCs can be rapidly expanded by this simple gene transfer method, which has numerous potential applications.

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Peretz, Y., Zhou, Z. F., Halwani, F., & Prud’homme, G. J. (2002). In vivo generation of dendritic cells by intramuscular codelivery of FLT3 ligand and GM-CSF plasmids. Molecular Therapy, 6(3), 407–414. https://doi.org/10.1006/mthe.2002.0677

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