Efficient induction of CD8 T-associated immune protection by vaccination with mRNA transfected dendritic cells.
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. Naive 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.
Zarei
Shohreh
S
Allergy Unit, Division of Immunology and Allergy, University Hospital, Geneva Switzerland.
Arrighi
Jean-François
JF
Ongaro
Gioele
G
Calzascia
Thomas
T
Haller
Olivier
O
Frossard
Christophe
C
Piguet
Vincent
V
Walker
Paul R
PR
Hauser
Conrad
C
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000517:prevention & control*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger; D014162:Transfection; D019076:Transgenes / Q000235:genetics / Q000276:immunology; D014611:Vaccination
D018984:Epitopes, T-Lymphocyte; D012333:RNA, Messenger