title: Immunotherapy with oligomannose-coated liposomes ameliorates allergic symptoms in a murine food allergy model.
abstract: BACKGROUND
  Allergen-specific immunotherapy has been anticipated to be a disease-modifying therapy for food allergies. We previously reported that CD8(+) regulatory T cells may prevent antigen-sensitized mice from developing allergic diarrhea. Because oligomannose-coated liposomes (OML) have been shown to induce MHC class I-restricted CD8(+) T cell responses, we analyzed the adjuvant activities of OML for inducing regulatory CD8(+) T cells and mucosal tolerogenic responses in allergen-sensitized mice.
  
  
  METHODS
  The BALB/c mice that were previously sensitized to ovalbumin (OVA) were intranasally immunized with OVA-encased in OML (OVA-OML) or OVA-encased in non-coated liposomes (OVA-NL). We assessed allergic diarrhea induced by oral OVA administration, OVA-specific immunoglobulin production, and cytokine production in the intestines and mesenteric lymph nodes (MLNs).
  
  
  RESULTS
  Intranasal immunization with OVA-OML, but not OVA-NL, suppressed the development of allergic diarrhea. This was associated with in vitro Ag-induced IL-10 production and the in vivo expansion of CD8(+) CD28(-) and CD4(+) CD25(+) Foxp3(+) T cell populations among mesenteric lymph node mononuclear cells, and was significantly ablated by anti-SIGNR1 or anti-CR3 mAbs. Up-regulation of serum OVA-specific IgE was suppressed, whereas OVA-specific IgG1, IgG2a, and soluble IgA production were enhanced by intranasal administration of OVA-OML. Adoptive transfer of CD8(+) CD28(-) T cells but not CD28(+) CD8(+) T cells from the MLNs of OVA-OML-treated mice ameliorated the development of diarrhea.
  
  
  CONCLUSIONS
  These results suggest that intranasal immunization with Ag-encased OML may be an effective immunotherapy for food allergies, as it induces a subset of regulatory CD8(+) T cells as well as CD4(+) CD25(+) Foxp3(+) T cell and modulates humoral immune responses in allergen-sensitized mice.
authors.affiliation: Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawakita
authors.forename: Hisako
authors.initials: H
authors.lastname: Shirasaki
authors.forename: Motoko
authors.initials: M
authors.lastname: Yasutomi
authors.forename: Shuko
authors.initials: S
authors.lastname: Tokuriki
authors.forename: Mitsufumi
authors.initials: M
authors.lastname: Mayumi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
authors.forename: Yusei
authors.initials: Y
authors.lastname: Ohshima
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D003967:Diarrhea / Q000628:therapy; D004195:Disease Models, Animal; D005512:Food Hypersensitivity / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008081:Liposomes / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000276:immunology / Q000627:therapeutic use*; D010047:Ovalbumin / Q000276:immunology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D009844:Oligosaccharides; C028569:oligomannoside; D010047:Ovalbumin