CD4+TH2, not TH17 cells mount antigen specific recall response and drive allergic inflammation (P6029)

Abstract

Abstract Allergic asthma is a heterogeneous inflammatory disease of the airway. In addition to CD4+ TH2 and TH17 cells of the adaptive immunity, recently described innate lymphoid cells (ILC2) also contribute to the pathogenesis of allergic asthma. However, it remains unclear that which cell type is responsible for mounting antigen-driven immune response at the recall phase of allergic inflammation. Repeated intranasal OVA re-challenges induced a significant expansion of TH2, not TH17 or ILC2 cells in rested mice that were previously sensitized with OVA plus papain. Consequently, the amount of IL-5 and IL-13, not IL-17 or IFN-γ production in the lung of mice re-exposed to OVA antigen were significantly elevated than those of mice sensitized only. Mice ablated of CD4+ T cells failed to respond to repeated OVA antigen re-challenges and exhibited ameliorated allergic airway inflammation, while their lung ILC2 remained intact. Furthermore, STAT6-deficient mice that lacked TH2 cells also failed to mount allergic recall response to OVA antigen, despite of their competency in eliciting TH17 immune response. Collectively, our results suggest that lung resident antigen specific CD4+TH2 cells, not TH17 or ILC2 cells, induced after sensitization are the primary cell type responsible for mounting allergen recall response that exacerbates allergic inflammation.