Development of Th1 and Th2 lymphocytes. Antigens enter through the endobronchial tree, cross the epithelial surface, and interact with naive Th cells and DCs. As a result of signals from the surrounding microenvironment, they differentiate into Th1 cells, which produce IFN-γ, IL-2, and lymphotoxin (LT), or Th2 cells, which produce IL-4, IL-5, IL-9, IL-13, and IL-10. Polarization into Th1 cells occurs via a STAT-1– and T-bet–dependent pathway under the influence of CD8α+ DCs and macrophage-derived cytokines such as IFN-γ, IL-12, and IL-18. Differentiation into Th2 cells occurs via a pathway that involves STAT-6, GATA-3, nuclear factor of activated T cells-c (NFATc), and c-maf under the influence of CD8α– DCs and IL-4, which may come from mast cells.