Contribution of IRF-3 mediated IFNbeta production to DNA vaccine dependent cellular immune responses.
The mechanism(s) by which DNA vaccines activate Ag-specific cellular immune responses is incompletely understood. Current findings indicate that IRF-3 plays an important role in this process. The IRF-3 dependent signaling pathway is triggered by the presence of intracytoplasmic DNA, and culminates in the production of type I IFNs. DNA vaccination of IRF-3 KO mice elicits a strong Ag-specific humoral response, yet CD4 and CD8 T cell responses (including the production of Th1, Th2 and Th 17 cytokines) are severely impaired. Although expression of the immunogenic protein encoded by the DNA vaccine was similar in IRF-3 KO vs wild type mice, antigen presentation was severely impaired in the KO animals. This defect was remedied by the co-delivery of an IFNbeta encoding plasmid. These findings suggest that the IRF-3/IFNbeta pathways are key to the induction of cellular immunity following DNA vaccination.
Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD, 21702, United States.
Hidekazu
H
Shirota
Lev
L
Petrenko
Toshio
T
Hattori
Dennis M
DM
Klinman
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D007111:Immunity, Cellular / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics*; D016899:Interferon-beta / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010957:Plasmids / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D019444:Vaccines, DNA; D016899:Interferon-beta