Distribution fate and mechanism of immune modulation following mucosal delivery of plasmid DNA encoding IL-10.
DNA vaccination has been widely studied in several models of vaccination and in the treatment of inflammatory diseases, even though the mechanism involved is still unclear. This report demonstrates that mucosal administration of plasmid DNA leads to rapid and widespread distribution around the body. Dissemination likely occurred via the bloodstream because plasmid DNA was present in blood plasma. The plasmid DNA was also detectable in several tissues including draining lymph nodes, spleen, liver, bone marrow, and even the dermis of ear pinnae. Except for the site of administration, plasmid DNA was no longer detectable in tissues after 3 wk postadministration. RNA and protein expression was also found in the tissues and bloodstream. Animals previously primed by HSV infection and subsequently given IL-10 DNA via the nasal mucosa, showed diminished Ag-induced delayed type hypersensitivity reactions for up to 5 wk posttreatment. The mechanism of modulation involved diminished the Ag-specific proliferation and production of Th1 cytokines. The Ag-specific silencing effects persisted beyond the duration of detectable plasmid encoded protein and was maintained upon adoptive transfer of T cells into a plasmid-free environment. The silenced T cells were not a source of IL-10, and their anergic state was reversible by exposure to Ag in the presence of exogenous IL-2.
Chun
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Department of Microbiology, University of Tennessee, Knoxville 37996, USA.
Daheshia
M
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Lee
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Eo
S K
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Rouse
B T
BT
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009297:Nasal Mucosa / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D018139:Simplexvirus / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014018:Tissue Distribution / Q000235:genetics / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D016753:Interleukin-10