title: Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway.
abstract: Using a combination of local gene delivery and tolerizing DNA vaccination, we demonstrate that codelivery of the interleukin-4 (IL-4) gene and a DNA vaccine encoding the self-peptide proteolipid protein 139-151 (PLP139-151) provides protective immunity against experimental autoimmune encephalomyelitis (EAE). We provide evidence for a mechanism whereby IL-4 expressed from the naked DNA is secreted and acts locally on autoreactive T cells via activation of STAT6 to shift their cytokine profile to T helper 2. We also show that DNA vaccines can be used to reverse established EAE by covaccination with the genes for myelin oligodendrocyte glycoprotein and IL-4. This treatment strategy combines the antigen-specific effects of DNA vaccination and the beneficial effects of local gene delivery.
authors.affiliation: Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: H
authors.initials: H
authors.lastname: Garren
authors.forename: P J
authors.initials: PJ
authors.lastname: Ruiz
authors.forename: T A
authors.initials: TA
authors.lastname: Watkins
authors.forename: P
authors.initials: P
authors.lastname: Fontoura
authors.forename: L T
authors.initials: LT
authors.lastname: Nguyen
authors.forename: E R
authors.initials: ER
authors.lastname: Estline
authors.forename: D L
authors.initials: DL
authors.lastname: Hirschberg
authors.forename: L
authors.initials: L
authors.lastname: Steinman
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D050800:STAT6 Transcription Factor; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D019444:Vaccines, DNA; D015847:Interleukin-4