Immunotherapy with oligomannose-coated liposomes ameliorates allergic symptoms in a murine food allergy model

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. Conclusion: 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.