title: Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model.
abstract: BACKGROUND
  Human studies have demonstrated that allergen immunotherapy induces memory suppressive responses and IL-10 production by allergen-specific T cells. Previously, we established a mouse model in which allergen immunotherapy was effective in the suppression of allergen-induced asthma manifestations.
  
  
  OBJECTIVE
  In this study, we examined whether immunotherapy induces a long-lasting effect and investigated the role of IL-10 in successful immunotherapy.
  
  
  METHODS
  Ovalbumin-sensitized BALB/c mice were treated with 3 injections of ovalbumin (1 mg, subcutaneous) on alternate days. After a short interval (1 week) and after a long interval (5 weeks), mice were challenged by ovalbumin inhalation, and subsequently, airway reactivity, airway eosinophilia, ovalbumin-specific IgE, and T(H)2 cytokine profile were measured. Flow cytometry and blocking of IL-10 receptors in vivo were used to gain insight in the role of IL-10 in the beneficial effects of allergen immunotherapy.
  
  
  RESULTS
  After a long interval between ovalbumin immunotherapy and ovalbumin challenge, the development of airway eosinophilia and hyperresponsiveness to methacholine were as strongly suppressed as after a short interval. These suppressive effects coincided with significantly reduced serum ovalbumin-specific IgE levels and T(H)2 cytokine production. On immunotherapy, the IL-5:IL-10 ratio in the bronchoalveolar lavage fluid shifted toward IL-10. In ovalbumin-restimulated lung cell and thoracic lymph node cultures from these mice, IL-5 levels dramatically decreased, whereas the percentage of IL-10(+)CD4(+) T cells was not affected. Finally, in mice treated with mAb against IL-10 receptors, the beneficial effects of immunotherapy were largely abrogated.
  
  
  CONCLUSIONS
  These data demonstrate that allergen immunotherapy induces a memory suppressive effect in which IL-10 is essential.
authors.affiliation: Department of Pharmacology and Pathophysiology, Faculty of Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
authors.forename: Joost L M
authors.initials: JL
authors.lastname: Vissers
authors.forename: Betty C A M
authors.initials: BC
authors.lastname: van Esch
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Hofman
authors.forename: Martien L
authors.initials: ML
authors.lastname: Kapsenberg
authors.forename: Frank R
authors.initials: FR
authors.lastname: Weller
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: van Oosterhout
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D003888:Desensitization, Immunologic; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000502:physiology*; D015848:Interleukin-5 / Q000032:analysis; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
chemical_list: D016207:Cytokines; D015848:Interleukin-5; D016753:Interleukin-10; D007073:Immunoglobulin E; D010047:Ovalbumin