Immunomodulation by mucosal gene transfer using TGF-beta DNA.
This report evaluates the efficacy of DNA encoding TGF-beta administered mucosally to suppress immunity and modulate the immunoinflammatory response to herpes simplex virus (HSV) infection. A single intranasal administration of an eukaryotic expression vector encoding TGF-beta1 led to expression in the lung and lymphoid tissue. T cell-mediated immune responses to HSV infection were suppressed with this effect persisting as measured by the delayed-type hypersensitivity reaction for at least 7 wk. Treated animals were more susceptible to systemic infection with HSV. Multiple prophylactic mucosal administrations of TGF-beta DNA also suppressed the severity of ocular lesions caused by HSV infection, although no effects on this immunoinflammatory response were evident after therapeutic treatment with TGF-beta DNA. Our results demonstrate that the direct mucosal gene transfer of immunomodulatory cytokines provides a convenient means of modulating immunity and influencing the expression of inflammatory disorders.
Department of Microbiology, The University of Tennessee, Knoxville, Tennessee 37996-0845, USA.
N A
NA
Kuklin
M
M
Daheshia
S
S
Chun
B T
BT
Rouse
D000281:Administration, Intranasal; D000818:Animals; D002522:Chlorocebus aethiops; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa; D010957:Plasmids; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000494:pharmacology; D014709:Vero Cells
D016212:Transforming Growth Factor beta; D004247:DNA