Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model.
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.
Vissers
Joost L M
JL
Department of Pharmacology and Pathophysiology, Faculty of Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
van Esch
Betty C A M
BC
Hofman
Gerard A
GA
Kapsenberg
Martien L
ML
Weller
Frank R
FR
van Oosterhout
Antoon J M
AJ
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
D016207:Cytokines; D015848:Interleukin-5; D016753:Interleukin-10; D007073:Immunoglobulin E; D010047:Ovalbumin