Helper CD4+ T cells for IgE response to a dietary antigen develop in the liver

Background: Although T-cell responses to food antigens are normally inhibited either by deletion, active suppression, or both of antigen-specific T cells, T helper cells for IgE response to a food antigen still develop by unknown mechanisms in a genetically susceptible host. Objective: We determined the site at which those IgE helper T cells develop. Methods: We administered ovalbumin (OVA) orally to DO11.10 mice and studied CD4(+) T cells in Peyer's patches, the spleen, and the liver. Helper activity for IgE response was assessed by adoptively transferring those CD4(+) T cells to naive BALB/c mice, followed by systemic immunization with OVA. Results: OVA-specific CD4(+) T cells were deleted by cell death in the liver and Peyer's patches of DO11.10 mice fed OVA. OVA-specific CD4(+) T cells that survived apoptosis in the liver expressed Fas ligand and secreted IL-4, IL-10, and transforming growth factor beta(1). CD4(+) T cells producing IFN-gamma were deleted in the liver by repeated feeding of OVA. On transfer of CD4(+) T cells to naive mice and systemic immunization with OVA, a marked increase in OVA-specific IgE response developed only in the mice that received hepatic CD4(+) T cells from OVA-fed mice, the effect of which was not observed in the recipients of hepatic CD4+ T cells deficient in IL-4. In addition, significant suppression of delayed-type hypersensitivity and IgG(1)/IgG(2a) responses to OVA was observed in the recipients of hepatic CD4(+) T cells, and this suppression required Fas/Fas ligand interaction. Conclusion: Together, these results suggested that a food antigen might negatively select helper T cells for IgE response to the antigen by preferential deletion of T(H)1 cells in the liver. (J Allergy Clin Immunol 2003;111:1375-85.).