Immunomodulation by mucosal gene transfer using TGF-beta DNA.

N A Kuklin; M Daheshia; S Chun; B T Rouse

doi:10.1172/jci2803

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Immunomodulation by mucosal gene transfer using TGF-beta DNA.

N A Kuklin·M Daheshia·S Chun·B T Rouse

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Abstract

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.

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Administration, Intranasal Animals Chlorocebus aethiops DNA Disease Models, Animal Female Gene Expression Gene Transfer Techniques Herpes Simplex Humans Mice Mice, Inbred BALB C Nasal Mucosa Plasmids Transforming Growth Factor beta Vero Cells Journal Article Research Support, U.S. Gov't, P.H.S.

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N A Kuklin, M Daheshia, S Chun, B T Rouse. 1998-07-15. Immunomodulation by mucosal gene transfer using TGF-beta DNA.. https://doi.org/10.1172/jci2803

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