Methods: Naïve mice were exposed intranasally to natural allergens. Development of allergic immune responses was analyzed by collecting draining lymph nodes (LNs) and sera and by challenging mice with an antigen.
Results: Airway exposure of IL-4 reporter 4get mice to natural allergens, such as Alternaria and house dust mite, induced IL-4-competent Tfh and Th2 cells in various frequencies. Exposure of wild-type mice to Alternaria spiked with ovalbumin (OVA) induced OVA-specific IgE in the sera, and cells from LNs produced type 2 cytokines (i.e. IL-5, IL-13) when cultured with OVA. ICOS knockout and CD4-specific Bcl6 conditional knockout mice (both of which are deficient in Tfh cells while Th2 cells remain intact) developed significantly reduced serum levels of IgE antibody; however, LN cells from these mice produced robust type 2 cytokines when cultured with OVA. In contrast, OX40L knockout mice were deficient in type 2 cytokine responses and eosinophilic airway inflammation, but they developed levels of IgE antibody comparable to those of wild-type mice.
Conclusions: Tfh cells, but unlikely Th2 cells, are indispensable for IgE antibody production to airborne allergens. Type 2 cytokine responses and IgE antibody responses can be regulated independently by two different subsets of CD4+ T cells.