The Molecular Basis of Th2 Development

In response to antigen stimulation, naïve T helper (Th) cells develop into highly polarized effector cells that mediate effective immune responses. Th1 cells promote cellular immunity and are characterized by the production of IFN-γ, whereas Th2 cells are important for humoral immunity and produce IL-4, IL-5, and IL- 13. Both Th1- and Th2-mediated immunities are important for the host's defense against infections. However, unbalanced Th1 and Th2 responses cause autoimmune and allergic diseases, respectively. Many factors, such as the type of antigen, antigen affinity or dose, costimulation signals and the cytokine milieu influence the Th1/Th2 balance. For example, IL-12 and IFN-γ are strong Th1-promoting cytokines, whereas IL-4 and IL-6 are cytokines that drive Th2 development. In addition, tissue-specific transcription factors exist that determine the commitment of Th1 and Th2 cells for the production of distinct profiles of cytokines. Recently, it has been shown that antigen presenting cells can instruct T-cell differentiation via a cytokine-independent Notch signaling pathway. Although much knowledge has been gained during the last decade about the molecular mechanisms that drive Th1/Th2 differentiation, many questions still remain open.