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Insect bite hypersensitivity (IBH) in horses is a seasonal, IgE-mediated, pruritic skin disorder primarily caused by Culicoides spp.We hypothesize that a mixed Th2/Th1-type immune status, off season, alters into Th2-dominated immune reactivity in the skin of IBH-affected ponies in the IBH season. 2To study these immune response patterns Culicoides-specific IgE levels, skin histopathology and cytokine and transcription factor mRNA expression (IL4, IL10, IL13, IFNγ, FoxP3 and CD3 ζ ) in lesional and non-lesional skin of ponies affected by IBH in the IBH season were compared with those of the same animals off season and those in skin of healthy ponies in both seasons.The present study revealed a significantly higher histopathology score in lesional skin of affected ponies than in non-lesional skin and skin of healthy ponies in the IBH season. C. obsoletus-specific IgE serum levels of ponies with IBH were significantly higher than those in healthy ponies in both seasons. obsoletus-specific IgE did not correlate with higher histological scores in LE skin.In summary, our data indicate a general immune activation in the skin of both healthy and IBH-affected ponies during the IBH season that potentially obscures the Culicoides-specific immune reaction pattern, even in lesional skin of IBHaffected animals.3

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.

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The recombinant C. obsoletus complex allergens can stimulate antigen-specific Th1 and IL10 producing Treg cells and are therefore promising candidates for the immunotherapy of IBH.