Th2 cells mediate the activation and maintenance of the humoral, or antibody-mediated, immune response against extracellular parasites, bacteria, allergens, and toxins. Th2 cells mediate these functions by producing various cytokines such as IL-4, IL-5, IL-6, IL-9, IL-13, and IL-17E (IL-25) that are responsible for strong antibody production, eosinophil activation, and inhibition of several macrophage functions, thus providing phagocyte-independent protective responses. These cytokines also counteract the Th1 responses that allow for the Th2 responsiveness to IL-4. IL-4 signals through STAT6 to upregulate GATA3 expression, the master regulator of Th2 cell differentiation. Repression of this activity results in the development failure of IL-4 producing cells. IL-4 also suppresses Th1 and Th17 cell responses through the upregulation of transcriptional repressor(s) of IFNγ and IL-17 production. However, the IL-4/STAT6 pathway is not completely essential for Th2 cell differentiation as Th2 cell differentiation can also occur through other cytokines such as TSLP, IL-17E (IL-25), and IL-33. Regardless, GATA3 expression and STAT5 activation, most commonly through IL-2 for Th2 cells, is completely essential for Th2 cellular differentiation.

Relevant Recombinant Proteins

  • IL-2
    • Expressed by activated T cells, but not by resting T cells
    • Mediates their proliferation and clonal expansion
  • IL-4
    • Required for Th2 priming and maturation
    • An autocrine of Th2 cells during their maturation
    • High concentrations can block the generation of Th1 cells from naïve T cells
  • IL-6
    • Initiates maturation of Th2 cells from TH0 in conjunction with IL-4
    • High concentration can block the generation of Th1 cells in a similar fashion to IL-4
  • IL-31
    • Associated with enhanced IL-4 and IL-13 expression by Th2
  • IL-33
    • Necessary for Th2 cytokine production
  • TSLP
    • Drives Th2 differentiation via the induction of IL-4 production

Relevant Neutralizing Antibodies

  • Anti- IFN-gamma and Anti- IL-12/IL-23p40
    • Prevents inhibition of Th2 differentiation and promotion of Th1 differentiation