title: Dose-response relationship of specific allergen exposure-induced immunological tolerance: a mouse model.
abstract: BACKGROUND
  It is believed that adequate allergen preimmunization exposure could induce immunologic tolerance. The purpose of this study was to investigate the dose-dependent mechanisms related to antigen-specific tolerance induction in a mouse model.
  
  
  METHODS
  Mice were assigned to 5 groups: the control (Cont) group received phosphate-buffered saline (PBS) preimmunization exposure and PBS sham immunization; the other 4 groups were exposed preimmunization to PBS (PBS group) or ovalbumin (OVA) (first mucosal doses: 1.25%, 2.5%, or 5% wt/vol aerosol from days -3 to -1) prior to OVA immunization. The OVA-immunized mice received intraperitoneal doses of 20 μg OVA (on days 1, 7, and 14), and then a second set of mucosal doses with 0.5% wt/vol OVA aerosol (on days 18 to 20). After assessment of airway hyperresponsiveness (AHR), the mice were euthanized and their blood, bronchoalveolar lavage fluids (BALFs), and lung tissues were collected for further analyses.
  
  
  RESULTS
  OVA-immunized mice exposed to OVA preimmunization had reduced AHR and immunoglobulin E production when compared to the PBS group. OVA preimmunization exposure inhibited eosinophilic inflammation in lung tissues. The proportions of BALF eosinophil counts from the groups exposed to OVA preimmunization were significantly decreased when compared with those exposed to PBS preimmunization. The balance of T helper 2 (Th2) and T regulatory (Treg) cytokines in BALFs were additionally observed in this mouse model.
  
  
  CONCLUSIONS
  Our results suggest that preimmunization exposure to an appropriate dose of a specific antigen could suppress allergic airway inflammation by induction of immunological tolerance.
authors.affiliation: Department of Natural Biotechnology, Nanhua University, Chiayi, Taiwan.
authors.forename: Yueh-Chiao
authors.initials: YC
authors.lastname: Yeh
authors.affiliation: Research Center for Traditional Chinese Medicine, Department of Medical Research and Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.|Research Center for Chinese Medicine and Acupuncture, and School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Hung-Rong
authors.initials: HR
authors.lastname: Yen
authors.affiliation: Department of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Rong-San
authors.initials: RS
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Ren-Ching
authors.initials: RC
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Shyh-Chang
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Research Center for Chinese Medicine and Acupuncture, and School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Bo-Shiou
authors.initials: BS
authors.lastname: Lin
authors.affiliation: Department of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Medicine, National Yang-Ming Medical University, Taipei, Taiwan.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Liang
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D016207:Cytokines / Q000276:immunology; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D047093:Eosinophil Major Basic Protein / Q000276:immunology; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin; D047093:Eosinophil Major Basic Protein
keywords: aeroallergens; allergens; allergy immunotherapy; asthma; inhalation allergen challenge