title: Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity.
abstract: The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus). We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFNγ mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFNγ-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Chantal
authors.initials: C
authors.lastname: Meulenbroeks
authors.affiliation: IDEXX Laboratories, Hoofddorp, The Netherlands.
authors.forename: Jaco J
authors.initials: JJ
authors.lastname: van der Lugt
authors.affiliation: Department of Cell Biology & Immunology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Nathalie M A
authors.initials: NM
authors.lastname: van der Meide
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Willemse
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Pretoria, Onderstepoort, South Africa.
authors.forename: Victor P M G
authors.initials: VP
authors.lastname: Rutten
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, EH9 3JT, United Kingdom.
authors.forename: Dietmar M W
authors.initials: DM
authors.lastname: Zaiss
mesh_terms: D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002519:Ceratopogonidae / Q000145:classification* / Q000276:immunology; D006736:Horses; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance; D007299:Insect Bites and Stings; D007371:Interferon-gamma / Q000276:immunology
chemical_list: D000485:Allergens; D000906:Antibodies; D007371:Interferon-gamma