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Immunotherapy with oligomannose‐coated liposomes ameliorates allergic symptoms in a murine food allergy model
Author(s) -
Kawakita Akiko,
Shirasaki Hisako,
Yasutomi Motoko,
Tokuriki Shuko,
Mayumi Mitsufumi,
Naiki Hironobu,
Ohshima Yusei
Publication year - 2012
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2011.02777.x
Subject(s) - ovalbumin , immunology , adoptive cell transfer , allergy , nasal administration , mesenteric lymph nodes , allergen , immune system , t cell , antigen , adjuvant , medicine , biology
Background: Allergen‐specific immunotherapy has been anticipated to be a disease‐modifying therapy for food allergies. We previously reported that CD 8 + 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 CD 8 + T cell responses, we analyzed the adjuvant activities of OML for inducing regulatory CD 8 + 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 ( MLN s). Results: Intranasal immunization with OVA ‐ OML , but not OVA ‐ NL , suppressed the development of allergic diarrhea. This was associated with in vitro A g‐induced IL ‐10 production and the in vivo expansion of CD 8 + CD 28 − and CD 4 + CD 25 + F oxp3 + T cell populations among mesenteric lymph node mononuclear cells, and was significantly ablated by anti‐ SIGNR 1 or anti‐ CR 3 m A bs. Up‐regulation of serum OVA ‐specific I g E was suppressed, whereas OVA ‐specific I g G 1, I g G 2a, and soluble I g A production were enhanced by intranasal administration of OVA ‐ OML . Adoptive transfer of CD 8 + CD 28 − T cells but not CD 28 + CD 8 + T cells from the MLN s of OVA ‐ OML ‐treated mice ameliorated the development of diarrhea. Conclusion: These results suggest that intranasal immunization with A g‐encased OML may be an effective immunotherapy for food allergies, as it induces a subset of regulatory CD 8 + T cells as well as CD 4 + CD 25 + F oxp3 + T cell and modulates humoral immune responses in allergen‐sensitized mice.