Suppression of Specific and Bystander IgE Responses in a Mouse Model of Oral Sensitization to β-Lactoglobulin

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Abstract
Background: Mechanisms of systemic IgE suppression by oral tolerance have been extensively studied, but less is known about oral tolerance induction in mice challenged at mucosal sites. We have previously shown in systemically challenged mice that high-dose tolerance suppressed specific but not bystander IgE. In an attempt to mimic oral tolerance in food-allergic patients, we have investigated how IgE suppression could be induced in mice sensitized orally against β-lactoglobulin (BLG). Methods: Mice were immunized orally against BLG using cholera toxin as adjuvant. Before oral sensitization, mice were administered milk whey proteins, either in the form of a single high-dose gavage, or by prolonged ad libitum administration of various doses. Results: Orally sensitized mice mounted a BLG-specific IgE response. In contrast to systemically challenged mice, a single high-dose gavage of whey protein given prior to the onset of oral sensitization resulted in the suppression of both specific and bystander IgE. When mice were fed moderate to low doses of milk whey proteins daily ad libitum in the drinking water during 3 weeks prior to oral sensitization, all doses effectively suppressed antigen-specific IgE. However, bystander IgE suppression was observed only at the lowest doses. When mice were tolerized during 4 days instead of 3 weeks, IgE titers remained unchanged. Conclusions: In orally sensitized mice, bystander IgE suppression depended on the dose of tolerogen, but also on its mode of administration. Mucosally induced IgE responses were suppressed by a mechanism that was distinct from that operating in the periphery.