Characterization of an endogenous Th17-cell generation during sensitization in the murine lung

We could show in previous studies that an ongoing Th17-polarized pulmonary inflammation poses a risk for further sensitziations. In concurrence with this process, we observed the generation of endogenous antigen specific T cell populations, which produced either interleukin-17 (IL-17) or interferon-gamma (IFNg). We strove to determine location and time of endogenous T cell generation, as well as analyze its respective phenotype. We used a murine model of Th17-dependent airway inflammation by adoptive transfer of polarized T cells and two subsequent intranasal challenge phases, by which pulmonary sensitization towards a new antigen is induced. In order to analyze endogenous Th17 cell induction, we took advantage of transgenic reporter animals, expressing GFP and Th17-specific transcription factor RORgamma-t. Flow-cytometric analyses revealed that after both challenge phases the percentage of IL-17-and IFNg-producing cells was higher in lung compared to draining lymph nodes (LN). However, the ratio between IL-17+ cells to IFNg+ cells switched between the two inflammation phases. Endogenous Th17 cells (IL-17+GFP+CD4+) in the lung showed an increased expression of memory markers (CD62L, CCR7) compared to IFNg+ lung T-cells. Generation of endogenous Th17 cells could be detected as early as 48h after induction of Th17-polarized airway inflammation. Our data indicate that induction of IL-17+ T cells in the context of Th17-dependent pulmonary sensitization might take place primarily in the lung and not in the draining LNs and occurs prior to induction of IFNg+ T cells. Further investigations in this model will expand our knowledge about the mechanisms contributing to priming for airway allergens.