The polarization of T helper cells toward a Th1 phenotype is driven by which cytokines?

• A. IL-4 and IL-5
• B. IL-10 and TGF-β
• C. IL-17 and IL-22
• D. IL-12 and IFN-γ

Answer: (D)

Th1 differentiation happens when naive CD4+ T cells encounter a cytokine environment that includes IL-12 and IFN-γ. IL-12, produced by macrophages and dendritic cells in response to intracellular pathogens, activates its receptor on the developing T cells and signals through STAT4, promoting the transcription factor T-bet and steering the cells toward a Th1 program. IFN-γ, produced early by NK cells and later by Th1 cells, reinforces this differentiation and activates macrophages to heighten intracellular pathogen killing. Together, IL-12 and IFN-γ establish a Th1 response, which is geared toward cell-mediated immunity and intracellular pathogens. In contrast, other cytokines push toward Th2 (IL-4 is key), regulatory T cells (IL-10 and TGF-β), or Th17 (IL-17 and IL-22), so they do not drive Th1 polarization.