Generation of Th1 and Th2 cells from a naive CD4⁺ T cell. A naive CD4⁺ T cell does not secrete cytokines, and has low levels of GATA-3 and c-Maf expression. Differentiation along the Th1 or Th2 pathway is triggered by stimulation with antigen (Ag), presented to the T-cell receptor in the context of MHC by the appropriate APC, and by a second signal, imparted by ligation of costimulatory molecules B7-1/B7-2 and CD28. In the lung, DCs represent the key APC. The DCs have been classified into 2 subsets: mature (DC1) and immature (DC2). The mature DCs express high levels of MHC class II on their surface and produce IL-12, which drives Th1 differentiation. The immature DCs express low levels of MHC class II and produce IL-10, which favors Th2 differentiation. Furthermore, the cytokine(s) present in the microenvironment, IL-4/IL-10 versus IL-12, plays a decisive role in orchestrating the differentiation along the Th1 or Th2 lineage.