Immunologic characterization of 3 murine regimens of allergen-specific immunotherapy

Abstract

Allergen-specific immunotherapy (ASIT) is used to treat the symptoms of immediate type I hypersensitivity. The mechanisms driving establishment of allergen tolerance are not yet fully understood. The goal of this study was to develop and immunologically characterize 3 murine models of ASIT to simulate protocols currently used to treat patients with type I hypersensitivities. Ovalbumin (OVA)-sensitized mice were desensitized to OVA by means of repeated injections of OVA with a rapid, intermediate, or gradual protocol. After desensitization, mice were assessed for clinical sensitivity to OVA, and immunologic parameters were assessed. Mice in all treatment protocols displayed decreased vascular permeability in response to OVA challenge after desensitization. Circulating OVA-specific IgE levels, as well as basophil activation in response to OVA stimulation and IgE cross-linking, were significantly decreased in all treatment groups. Intermediate and gradual protocols, but not rapid desensitization, suppressed splenocyte proliferation and production of IL-4, IL-5, and IFN-γ in response to OVA and polyclonal activation. Similarly, significant increases in IL-10 production, numbers of CD4(+)CD25(+) forkhead box protein 3-positive regulatory T cells, and OVA-specific IgG1 antibody levels were only observed in mice undergoing prolonged ASIT regimens. Suppression of IgE-mediated activation is a common feature of all desensitization schedules. Induction of immunoregulatory networks requires prolonged desensitization schedules.