Serum IgE response to orally ingested antigen: a novel IgE response model with allergen-specific T-cell receptor transgenic mice.

Abstract

The mechanism by which orally ingested allergens elicit an IgE response remains unclear because there are few animal models available for investigation of this response. We tried to develop a murine model suitable for investigation of the IgE response to orally ingested allergens, which would allow us to identify T cells that could promote IgE production. Ovalbumin (OVA)-specific T-cell receptor transgenic mice were fed a diet containing OVA, and both the serum antibody response and cytokine production by splenocytes were examined. Oral administration of OVA to transgenic mice led to an increase in the levels of both antigen-specific IgE and total IgE in the sera. Subsequent intravenous challenge of OVA-fed transgenic mice with OVA resulted in anaphylactic shock. Analysis of cytokine production by splenocytes revealed that high IL-4-producing T cells appeared in the spleen 1 week after the start of feeding the OVA diet. T cells from these mice were found to promote IgE secretion by BALB/c B cells in vitro. This helper activity and the levels of IL-4 secretion were diminished after long-term feeding. These findings suggest the possibility that the orally ingested antigen elicited a response by a subpopulation of T cells that produce high levels of T(H2)-type cytokines and that promote IgE secretion, and these same T cells were tolerized by the orally ingested antigen. This experimental model with transgenic mice may be a useful tool for further studies of the cellular and molecular mechanisms of the T-cell and IgE responses to orally ingested antigens.