Initiation of food allergy by a CD4+ T cell-intrinsic IL-4 program, controlled by OX40L (P6204) Conference Paper uri icon

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abstract

  • Abstract Intestinal Th2 immunity in food allergy results in the production of IgG1 and IgE, and upon antigen challenge, anaphylaxis and eosinophilic inflammation. Although allergic sensitization critically requires IL-4 to develop, the source and control of IL-4 during the initiation of Th2 immunity remains unclear. Non-intestinal and non-food allergy systems have suggested a role for innate lymphocytes such as NKT or γδ T cells as a rapid source of IL-4 required to induce Th2 polarization. In contrast, we show here that NKT-deficient IL-15 KO, β2m KO and anti-NK1.1 treated mice have completely intact Th2 food allergic responses comparable to NKT-sufficient mice, including antigen-specific IgG1 and IgE, anaphylaxis, eosinophilic inflammation and cytokine production. Likewise, γδ T cell-deficient TCRδ KO mice mount comparable Th2 immune responses to oral antigen as their WT counterparts. By restricting IL-4 expression to only CD4+ Th cells, we find that IL-4 from CD4+ Th cells themselves induce food allergy. Further, IL-4 reporter mice show that CD4+ Th cell production of IL-4 in vivo is dependent on OX40L, a costimulatory molecule that we have shown to be highly expressed on allergen-exposed dendritic cells (DCs). Although NKT and γδ T cells express IL-4, this is not upregulated after allergen priming. Together, these data show that intestinal Th2 immunity in food allergy is initiated by a CD4+ Th cell-intrinsic IL-4 program that is controlled by DC-OX40L and not NKT or γδ T cells.

publication date

  • May 1, 2013