title: Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant bet v 1, the major birch pollen allergen, in a murine model of type I allergy.
abstract: BACKGROUND
  Mucosal (nasal or oral) administration of soluble protein antigens induces a state of antigen-specific immunologic hyporesponsiveness. Several studies have shown that induction of mucosal tolerance can prevent the onset or reduce the severity of certain TH1 -mediated experimental autoimmune diseases. Only a few studies describe similar results for type I allergies, which are caused by excessive TH2 cell activities.
  
  
  OBJECTIVE
  We sought to investigate whether mucosal tolerance induction would also be efficient in preventing an allergic type I immune response.
  
  
  METHODS
  A murine model of inhalative type I allergy, leading to sensitization to birch pollen and its major allergen Bet v 1 in BALB/c mice, was used. Recombinant Bet v 1 was nasally or orally applied in low doses before sensitization. At the time of death, immediate-type skin tests were performed. Blood was taken, and serum was used for measurement of allergen-specific antibodies. Spleen cell cultures were performed to determine cytokine production (IL-4, IL-5, IL-10, and IFN-gamma), as well as levels of TGF-beta mRNA.
  
  
  RESULTS
  Both nasal and oral administration of minimal doses of recombinant Bet v 1 before aerosol sensitization with birch pollen suppressed the allergen-specific antibody production of all isotypes. Consequently, the in vivo type I skin test responses to the allergen were negative in the tolerized, in contrast to the sensitized, group. Moreover, allergen-specific lymphoproliferative responses and cytokine production in vitro (ie, IFN-gamma, IL-4, IL-5, and IL-10) were markedly reduced. In contrast, expression of TGF-beta mRNA was markedly increased in spleen cells from nasally tolerized animals, indicating regulatory mechanisms for tolerance induction.
  
  
  CONCLUSIONS
  We conclude from the present study that nasal, as well as oral, administration of recombinant allergen is an effective way to prevent allergen-specific T- and B-cell responses in a TH2 model.
authors.affiliation: Institute of General and Experimental Pathology, Division of Immunopathology, University of Vienna, Austria.
authors.forename: U
authors.initials: U
authors.lastname: Wiedermann
authors.forename: B
authors.initials: B
authors.lastname: Jahn-Schmid
authors.forename: B
authors.initials: B
authors.lastname: Bohle
authors.forename: A
authors.initials: A
authors.lastname: Repa
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: D
authors.initials: D
authors.lastname: Kraft
authors.forename: C
authors.initials: C
authors.lastname: Ebner
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D052179:Antigens, Plant; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D000939:Epitopes; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D007108:Immune Tolerance; D007114:Immunization; D007132:Immunoglobulin Isotypes; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000008:administration & dosage* / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000276:immunology; D012882:Skin Tests; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D000939:Epitopes; D007132:Immunoglobulin Isotypes; D010940:Plant Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C061312:Bet v 1 allergen, Betula