title: Oral gene application using chitosan-DNA nanoparticles induces transferable tolerance.
abstract: Oral tolerance is a promising approach to induce unresponsiveness to various antigens. The development of tolerogenic vaccines could be exploited in modulating the immune response in autoimmune disease and allograft rejection. In this study, we investigated a nonviral gene transfer strategy for inducing oral tolerance via antigen-encoding chitosan-DNA nanoparticles (NP). Oral application of ovalbumin (OVA)-encoding chitosan-DNA NP (OVA-NP) suppressed the OVA-specific delayed-type hypersensitivity (DTH) response and anti-OVA antibody formation, as well as spleen cell proliferation following OVA stimulation. Cytokine expression patterns following OVA stimulation in vitro showed a shift from a Th1 toward a Th2/Th3 response. The OVA-NP-induced tolerance was transferable from donor to naïve recipient mice via adoptive spleen cell transfer and was mediated by CD4(+)CD25(+) T cells. These findings indicate that nonviral oral gene transfer can induce regulatory T cells for antigen-specific immune modulation.
authors.affiliation: Department of Internal Medicine 5-Hematology/Oncology and Institute for Clinical Immunology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. katja.goldmann@uk-erlangen.de
authors.forename: Katja
authors.initials: K
authors.lastname: Goldmann
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Ensminger
authors.forename: Bernd M
authors.initials: BM
authors.lastname: Spriewald
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D048271:Chitosan / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D007108:Immune Tolerance; D007155:Immunologic Factors / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D010047:Ovalbumin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000906:Antibodies; D016207:Cytokines; D004337:Drug Carriers; D007155:Immunologic Factors; D010047:Ovalbumin; D004247:DNA; D048271:Chitosan