Potential of transfected muscle cells to contribute to DNA vaccine immunogenicity.
The mechanism(s) by which DNA vaccines trigger the activation of Ag-specific T cells is incompletely understood. A series of in vivo and in vitro experiments indicates plasmid transfection stimulates muscle cells to up-regulate expression of MHC class I and costimulatory molecules and to produce multiple cytokines and chemokines. Transfected muscle cells gain the ability to directly present Ag to CD8 T cells through an IFN-regulatory factor 3-dependent process. These findings suggest that transfected muscle cells at the site of DNA vaccination may contribute to the magnitude and/or duration of the immune response initiated by professional APCs.
Shirota
Hidekazu
H
Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21702, USA.
Petrenko
Lev
L
Hong
Choongman
C
Klinman
Dennis M
DM
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010957:Plasmids; D052097:Quadriceps Muscle / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014162:Transfection / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D019444:Vaccines, DNA