Invariant NKT cells (iNKT cells) play a pivotal role in the development of allergen-induced airway hyperresponsiveness (AHR) and inflammation. However, it is unclear what role they play in the initiation (sensitization) phase as opposed to the effector (challenge) phase. The role of iNKT cells during sensitization was examined by determining the response of mice to intratracheal transfer of OVA-pulsed or OVA-α-galactosylceramide (OVA/αGalCer)- pulsed bone marrow-derived dendritic cells (BMDCs) prior to allergen challenge. Wild-type (WT) recipients of OVA-BMDCs developed AHR, increased airway eosinophilia, and increased levels of Th2 cytokines in bronchoalveolar lavage fluid, whereas recipients of OVA/αGalCer BMDCs failed to do so. In contrast, transfer of these same OVA/αGalCer BMDCs into IFN-γ-deficient (IFN-γ-/-) mice enhanced the development of these lung allergic responses, which was reversed by exogenous IFN-γ treatment following OVA-BMDC transfer. Further, Jα18-deficient recipients, which lack iNKT cells, developed the full spectrum of lung allergic responses following reconstitution with highly purified WT liver or spleen iNKT cells and transfer of OVA-BMDCs, whereas reconstituted recipients of OVA/αGalCer BMDCs failed to do so. Transfer of iNKT cells from IFN-γ-/- mice restored the development of these responses in Jα18-deficient recipients following OVA-BMDC transfer; the responses were enhanced following OVA/αGalCer BMDC transfer. iNKT cells from these IFN-γ-/- mice produced higher levels of IL-13 in vitro compared with WT iNKT cells. These data identify IFN-γ as playing a critical role in dictating the consequences of iNKT cell activation in the initiation phase of the development of AHR and airway inflammation.
ASJC Scopus subject areas
- Immunology and Allergy