Th2 Cells

T helper type 2 (Th2) cells are a distinct lineage of CD4⁺ effector T cell that secretes IL-4, IL-5, IL-9, IL-13, and IL-17E/IL-25. These cells are required for humoral immunity and play an important role in coordinating the immune response to large extracellular pathogens. Th2 differentiation occurs in the presence of IL-4 and either IL-2, IL-7, or Thymic Stromal Lymphopoietin (TSLP). Exposure of activated naive CD4⁺ T cells to IL-4 induces STAT6-dependent expression of GATA-3 and Growth Factor Independent-1 (GFI-1). GATA-3, the master transcriptional regulator of Th2 cells, promotes IL-5 and IL-13 expression, and along with GFI-1 stimulates the expansion of Th2 cells, while suppressing the differentiation of other T cell subtypes. In addition to IL-4-induced activation of GATA-3, IL-2, IL-7, or TSLP is required during Th2 differentiation to activate STAT5, which cooperates with GATA-3 to promote T cell production of IL-4. IL-4 regulates clonal expansion of Th2 cells, and along with IL-13, promotes B cell production of IgE and alternative macrophage activation. Other cytokines produced by Th2 cells stimulate eosinophil activation and survival (IL-5), or promote mast cell activation (IL-9). Under certain conditions, both IL-17E/IL-25 and IL-33 have also been shown to initiate or enhance Th2-like immune responses. In addition to the production of specific cytokines, Th2 cells are characterized by the expression of the cell surface receptors, ST2/IL-1 R4, CXCR4, CCR3, CCR4, and CCR8. Excessive Th2-type immune responses have been implicated in the development of chronic allergic inflammation and asthma.