Efficient Induction of CD8 T-Associated Immune Protection by Vaccination with mRNA Transfected Dendritic Cells

• Published in: Journal of investigative dermatology Vol. 121; no. 4; pp. 745 - 750
• Main Authors: Zarei, Shohreh, Arrighi, Jean-François, Ongaro, Gioele, Calzascia, Thomas, Haller, Olivier, Frossard, Christophe, Piguet, Vincent, Walker, Paul R., Hauser, Conrad
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.10.2003; Nature Publishing; Elsevier Limited
• Subjects: Animals; Antigen Presentation; Biological and medical sciences; CD8 T cells; CD8-Positive T-Lymphocytes - immunology; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - transplantation; Epidemiology. Vaccinations; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Female; General aspects; Infectious diseases; Lymphocytic Choriomeningitis - immunology; Lymphocytic Choriomeningitis - prevention & control; lymphocytic choriomeningitis virus; Lymphocytic choriomeningitis virus - immunology; Male; Medical sciences; Mice; Mice, Transgenic; mRNA transfection; RNA, Messenger; Transfection; Transgenes - genetics; Transgenes - immunology; Vaccination; dendritic cells; lymphocytic choriomeningitis virus; mRNA transfection; CD8 T cells; Dendritic cell; CD8 T cells/dendritic cells/lymphocytic choriomeningitis virus/mRNA transfection; Induction; Vaccination; Arenavirus; Virus; Immunoprophylaxis; Experimental disease; Messenger RNA; Lymphocytic choriomeningitis virus; Antigen presenting cell; T-Lymphocyte; Triggering; Arenaviridae
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.1523-1747.2003.12492.x

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-2Kb/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.