Dendritic cells are excellent targets for antigen-specific immune intervention. Here we attempted to introduce a CD8 T cell-dependent epitope into dendritic cells for presentation on major histocompatibility complex class I and induction of immunity. Murine bone-marrow-derived dendritic cells were subjected to electroporation with mRNA transcribed in vitro from a plasmid encoding lymphocytic choriomeningitis virus glycoprotein or enhanced green fluorescent protein under the control of a T7 promotor. The transfection efficiency of dendritic cells was 22 to 40%. Maturation was not inhibited by the electroporation. Dendritic cells electroporated with the appropriate antigen induced cell number-dependent in vitro proliferation in CD8 T cells expressing a transgenic receptor recognizing the 33 to 41 sequence of lymphocytic choriomeningitis virus glycoprotein in association with H-2K b/Db, indicating correct synthesis, processing, and presentation of the epitope. Naïve C57BL/6 mice vaccinated with electroporated dendritic cells and challenged with lymphocytic choriomeningitis virus were protected. Vaccination induced epitope-specific T cells as assessed by tetramer staining in blood and spleen. These results indicate that targeting dendritic cells with antigen-encoding mRNA can induce antigen-specific CD8 T cell responses as well as protective anti-viral immunity in vivo. Targeting dendritic cells with antigen-encoding mRNA may find wider application for immune intervention in disorders such as autoimmunity and cancer.
CITATION STYLE
Zarei, S., Arrighi, J. F., Ongaro, G., Calzascia, T., Haller, O., Frossard, C., … Hauser, C. (2003). Efficient Induction of CD8 T-Associated Immune Protection by Vaccination with mRNA Transfected Dendritic Cells. Journal of Investigative Dermatology, 121(4), 745–750. https://doi.org/10.1046/j.1523-1747.2003.12492.x
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