Potential strategies for inhibiting Th2 function in asthma. (a) Block Th2 cell differentiation. The cytokine environment that is present during CD4⁺ T-cell differentiation affects the development of new Th2 cells. Blocking IL-4 and/or IL-13 or the Th2-specific transcription factor GATA-3 leads to inhibition of Th2 cell induction. Alternatively, increasing levels of IL-12 and IFN-γ in the environment may shift the Th1/Th2 balance toward Th1 and reduce the number of Th2 cells in the respiratory tract. This can be accomplished by stimulating a Th1 response to certain infectious agents, such as Mycobacterium, or by the administration of CpG oligodeoxynucleotides. All of these interventions may have an effect in asthma by reducing the number of Th2 cells in the airways and by inhibiting the generation of new Th2 cells. (b) Block Th2 cell activation. Glucocorticoids are standard therapy in asthma and cause nonselective immunosuppression. Th2 cell activation may be selectively blocked using inhibitors of GATA-3, a T cell–specific factor that controls the production of key Th2 cytokines. (c) Block Th2 cytokine effects. Blocking IL-4, IL-5, or IL-13 may inhibit the effects of these cytokines on target tissues. In addition, Th1 cells have been shown to inhibit Th2 cytokine effects on eosinophils and airway epithelial mucus production. Allergy immunotherapy and CpG oligodeoxynucleotides both induce Th1 cells and lead to a reduction in allergic airway pathology.